Q96BT7 · ALKB8_HUMAN
- ProteinAlkylated DNA repair protein alkB homolog 8
- GeneALKBH8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids664 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain (PubMed:20123966, PubMed:20308323, PubMed:31079898).
Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966, PubMed:20308323).
Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys) (PubMed:20308323).
Binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly) (PubMed:21285950).
Required for normal survival after DNA damage (PubMed:20308323).
May inhibit apoptosis and promote cell survival and angiogenesis (PubMed:19293182).
Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966, PubMed:20308323).
Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys) (PubMed:20308323).
Binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly) (PubMed:21285950).
Required for normal survival after DNA damage (PubMed:20308323).
May inhibit apoptosis and promote cell survival and angiogenesis (PubMed:19293182).
Catalytic activity
- 5-(carboxymethyl)uridine34 in tRNA + S-adenosyl-L-methionine = 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA + S-adenosyl-L-homocysteine
Cofactor
Note: Binds 1 Fe2+ ion per subunit.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 227-229 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: NQY | ||||||
Binding site | 238 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 240 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 242 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 292 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 328 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 334 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 341 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 343 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 349 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | 2-oxoglutarate-dependent dioxygenase activity | |
Molecular Function | iron ion binding | |
Molecular Function | S-adenosylmethionine-dependent methyltransferase activity | |
Molecular Function | tRNA (5-carboxymethyluridine(34)-5-O)-methyltransferase activity | |
Molecular Function | tRNA (uridine) methyltransferase activity | |
Molecular Function | tRNA binding | |
Molecular Function | zinc ion binding | |
Biological Process | DNA damage response | |
Biological Process | tRNA methylation | |
Biological Process | tRNA wobble uridine modification |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAlkylated DNA repair protein alkB homolog 8
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96BT7
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Involvement in disease
Intellectual developmental disorder, autosomal recessive 71 (MRT71)
- Note
- DescriptionA form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT71 features include impaired intellectual development, global developmental delay, mildly delayed walking, poor language, seizures in the first years of life, and behavioral abnormalities.
- See alsoMIM:618504
Natural variants in MRT71
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_083119 | 554-664 | missing | in MRT71; missing tRNA wobble uridine modification |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_083119 | 554-664 | in MRT71; missing tRNA wobble uridine modification | |||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 787 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000337125 | 1-664 | Alkylated DNA repair protein alkB homolog 8 | |||
Sequence: MDSNHQSNYKLSKTEKKFLRKQIKAKHTLLRHEGIETVSYATQSLVVANGGLGNGVSRNQLLPVLEKCGLVDALLMPPNKPYSFARYRTTEESKRAYVTLNGKEVVDDLGQKITLYLNFVEKVQWKELRPQALPPGLMVVEEIISSEEEKMLLESVDWTEDTDNQNSQKSLKHRRVKHFGYEFHYENNNVDKDKPLSGGLPDICESFLEKWLRKGYIKHKPDQMTINQYEPGQGIPAHIDTHSAFEDEIVSLSLGSEIVMDFKHPDGIAVPVMLPRRSLLVMTGESRYLWTHGITCRKFDTVQASESLKSGIITSDVGDLTLSKRGLRTSFTFRKVRQTPCNCSYPLVCDSQRKETPPSFPESDKEASRLEQEYVHQVYEEIAGHFSSTRHTPWPHIVEFLKALPSGSIVADIGCGNGKYLGINKELYMIGCDRSQNLVDICRERQFQAFVCDALAVPVRSGSCDACISIAVIHHFATAERRVAALQEIVRLLRPGGKALIYVWAMEQEYNKQKSKYLRGNRNSQGKKEEMNSDTSVQRSLVEQMRDMGSRDSASSVPRINDSQEGGCNSRQVSNSKLPVHVNRTSFYSQDVLVPWHLKGNPDKGKPVEPFGPIGSQDPSPVFHRYYHVFREGELEGACRTVSDVRILQSYYDQGNWCVILQKA |
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed, with highest expression in spleen, followed by pancreas and lung.
Induction
Up-regulated after DNA damage. Induction is mediated via ATM.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with TRMT112.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q96BT7 | TRMT112 Q9UI30 | 10 | EBI-10825637, EBI-373326 | |
BINARY | Q96BT7-2 | ATN1 Q86V38 | 3 | EBI-13329511, EBI-11954292 | |
BINARY | Q96BT7-2 | KLK6 Q92876 | 3 | EBI-13329511, EBI-2432309 | |
BINARY | Q96BT7-2 | MFAP1 P55081 | 3 | EBI-13329511, EBI-1048159 | |
BINARY | Q96BT7-2 | PICK1 Q9NRD5 | 3 | EBI-13329511, EBI-79165 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 43-120 | RRM | ||||
Sequence: QSLVVANGGLGNGVSRNQLLPVLEKCGLVDALLMPPNKPYSFARYRTTEESKRAYVTLNGKEVVDDLGQKITLYLNFV | ||||||
Domain | 220-337 | Fe2OG dioxygenase | ||||
Sequence: KPDQMTINQYEPGQGIPAHIDTHSAFEDEIVSLSLGSEIVMDFKHPDGIAVPVMLPRRSLLVMTGESRYLWTHGITCRKFDTVQASESLKSGIITSDVGDLTLSKRGLRTSFTFRKVR | ||||||
Region | 411-664 | Methyltransferase domain | ||||
Sequence: ADIGCGNGKYLGINKELYMIGCDRSQNLVDICRERQFQAFVCDALAVPVRSGSCDACISIAVIHHFATAERRVAALQEIVRLLRPGGKALIYVWAMEQEYNKQKSKYLRGNRNSQGKKEEMNSDTSVQRSLVEQMRDMGSRDSASSVPRINDSQEGGCNSRQVSNSKLPVHVNRTSFYSQDVLVPWHLKGNPDKGKPVEPFGPIGSQDPSPVFHRYYHVFREGELEGACRTVSDVRILQSYYDQGNWCVILQKA | ||||||
Compositional bias | 515-534 | Basic and acidic residues | ||||
Sequence: SKYLRGNRNSQGKKEEMNSD | ||||||
Region | 515-575 | Disordered | ||||
Sequence: SKYLRGNRNSQGKKEEMNSDTSVQRSLVEQMRDMGSRDSASSVPRINDSQEGGCNSRQVSN | ||||||
Compositional bias | 535-575 | Polar residues | ||||
Sequence: TSVQRSLVEQMRDMGSRDSASSVPRINDSQEGGCNSRQVSN |
Sequence similarities
Belongs to the alkB family.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
Q96BT7-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length664
- Mass (Da)75,208
- Last updated2008-05-20 v2
- Checksum4BE595D6757C2A43
Q96BT7-2
- Name2
- NoteMay be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Q96BT7-3
- Name3
Q96BT7-4
- Name4
- NoteMay be due to competing donor splice site.
- Differences from canonical
- 1-1: M → MFAM
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
C9JQN2 | C9JQN2_HUMAN | ALKBH8 | 144 |
Features
Showing features for alternative sequence, sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_039159 | 1 | in isoform 4 | |||
Sequence: M → MFAM | ||||||
Sequence conflict | 210 | in Ref. 2; BAC04566 | ||||
Sequence: K → R | ||||||
Alternative sequence | VSP_033925 | 215-224 | in isoform 3 | |||
Sequence: GYIKHKPDQM → AEKNLEVGIH | ||||||
Alternative sequence | VSP_033926 | 225-664 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_033927 | 234-238 | in isoform 2 | |||
Sequence: GIPAH → DCHGF | ||||||
Alternative sequence | VSP_033928 | 239-664 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 515-534 | Basic and acidic residues | ||||
Sequence: SKYLRGNRNSQGKKEEMNSD | ||||||
Compositional bias | 535-575 | Polar residues | ||||
Sequence: TSVQRSLVEQMRDMGSRDSASSVPRINDSQEGGCNSRQVSN |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB218768 EMBL· GenBank· DDBJ | BAG16270.1 EMBL· GenBank· DDBJ | mRNA | ||
AK095523 EMBL· GenBank· DDBJ | BAC04566.1 EMBL· GenBank· DDBJ | mRNA | ||
AK293603 EMBL· GenBank· DDBJ | BAG57067.1 EMBL· GenBank· DDBJ | mRNA | ||
AK304413 EMBL· GenBank· DDBJ | BAG65244.1 EMBL· GenBank· DDBJ | mRNA | ||
AP001823 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471065 EMBL· GenBank· DDBJ | EAW67089.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471065 EMBL· GenBank· DDBJ | EAW67090.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC015183 EMBL· GenBank· DDBJ | AAH15183.1 EMBL· GenBank· DDBJ | mRNA |