B6CHA3 · UHRF1_XENLA
- ProteinE3 ubiquitin-protein ligase UHRF1
- Geneuhrf1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids772 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits dnmt1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins. However, it is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo.
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for site, binding site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Site | 314 | Histone H3K4me0 binding | |||
Site | 325 | Histone H3R2me0 binding | |||
Site | 328 | Histone H3R2me0 binding | |||
Binding site | 461-462 | 5-methylcytosine group (UniProtKB | ChEBI) of DNA (UniProtKB | ChEBI) | |||
Binding site | 467 | 5-methylcytosine group (UniProtKB | ChEBI) of DNA (UniProtKB | ChEBI) | |||
Site | 477 | Required to confer preferential recognition of cytosine over thymine | |||
Site | 487 | Required to discriminate between hemimethylated DNA versus symmetrically methylated DNA | |||
Site | 489 | Required for affinity and specificity for 5-mCpG sequence | |||
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chromatin | |
Cellular Component | euchromatin | |
Cellular Component | heterochromatin | |
Cellular Component | nucleus | |
Cellular Component | replication fork | |
Molecular Function | hemi-methylated DNA-binding | |
Molecular Function | histone binding | |
Molecular Function | methylated histone binding | |
Molecular Function | ubiquitin protein ligase activity | |
Molecular Function | ubiquitin-protein transferase activity | |
Molecular Function | zinc ion binding | |
Biological Process | heterochromatin formation | |
Biological Process | negative regulation of gene expression via chromosomal CpG island methylation | |
Biological Process | negative regulation of transcription by RNA polymerase II | |
Biological Process | protein ubiquitination | |
Biological Process | ubiquitin-dependent protein catabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase UHRF1
- EC number
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Amphibia > Batrachia > Anura > Pipoidea > Pipidae > Xenopodinae > Xenopus > Xenopus
Accessions
- Primary accessionB6CHA3
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes to replication foci. Enriched in pericentric heterochromatin. Also localizes to euchromatic regions (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000419989 | 1-772 | E3 ubiquitin-protein ligase UHRF1 | ||
Expression
Gene expression databases
Structure
Family & Domains
Features
Showing features for domain, region, zinc finger, compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Domain | 1-77 | Ubiquitin-like | |||
Region | 90-111 | Disordered | |||
Region | 129-205 | Tudor-like 1 | |||
Region | 212-281 | Tudor-like 2 | |||
Region | 291-299 | Linker | |||
Zinc finger | 297-364 | PHD-type | |||
Region | 331-335 | Histone H3R2me0 binding | |||
Region | 351-353 | Histone H3R2me0 binding | |||
Domain | 417-580 | YDG | |||
Region | 443-444 | Required to promote base flipping | |||
Region | 464-467 | Required for formation of a 5-methylcytosine-binding pocket | |||
Region | 476-479 | Required for formation of a 5-methylcytosine-binding pocket | |||
Compositional bias | 615-644 | Basic and acidic residues | |||
Region | 615-649 | Disordered | |||
Zinc finger | 703-742 | RING-type | |||
Domain
The tudor-like regions specifically recognize and bind histone H3 unmethylated at 'Arg-2' (H3R2me0), while the PHD-type zinc finger specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3).
The YDG domain (also named SRA domain) specifically recognizes and binds hemimethylated DNA at replication forks (DNA that is only methylated on the mother strand of replicating DNA).
The RING finger is required for ubiquitin ligase activity.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length772
- Mass (Da)86,974
- Last updated2008-11-25 v1
- MD5 Checksum6CC29C07318681782C4328EF079FA2E0
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Compositional bias | 615-644 | Basic and acidic residues | |||
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
EU177101 EMBL· GenBank· DDBJ | ABY28114.1 EMBL· GenBank· DDBJ | mRNA |