E7EZF3 · UHRF1_DANRE
- ProteinE3 ubiquitin-protein ligase UHRF1
- Geneuhrf1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids776 (go to sequence)
- Protein existenceEvidence at protein 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 (By similarity).
Required for pregastrula and lens development
Required for pregastrula and lens development
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 314 | Histone H3K4me0 binding | ||||
Sequence: C | ||||||
Site | 325 | Histone H3R2me0 binding | ||||
Sequence: P | ||||||
Site | 328 | Histone H3R2me0 binding | ||||
Sequence: Q | ||||||
Binding site | 461-462 | 5-methylcytosine group (UniProtKB | ChEBI) of DNA (UniProtKB | ChEBI) | ||||
Sequence: AG | ||||||
Binding site | 467 | 5-methylcytosine group (UniProtKB | ChEBI) of DNA (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Site | 477 | Required to confer preferential recognition of cytosine over thymine | ||||
Sequence: T | ||||||
Site | 487 | Required to discriminate between hemimethylated DNA versus symmetrically methylated DNA | ||||
Sequence: N | ||||||
Site | 489 | Required for affinity and specificity for 5-mCpG sequence | ||||
Sequence: R |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chromatin | |
Cellular Component | cytoplasm | |
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 | animal organ regeneration | |
Biological Process | heterochromatin formation | |
Biological Process | inflammatory response | |
Biological Process | intestinal epithelial structure maintenance | |
Biological Process | lens development in camera-type eye | |
Biological Process | liver development | |
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
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Actinopterygii > Neopterygii > Teleostei > Ostariophysi > Cypriniformes > Danionidae > Danioninae > Danio
Accessions
- Primary accessionE7EZF3
- Secondary accessions
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
Embryos have a small head, eyes, jaw and an underdeveloped gut. Moreover many mutants display diminished yolk consumption and uninflated swim bladder as well as embryonic lethality. DNA methylation is impaired during embryogenesis and embryos display defects in lens development and maintenance. No fertility defects are noted for heterozygous animals.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 649 | Non-phosphorylatable mutant; localizes only in nucleus and is unable to localize in cytoplasm. | ||||
Sequence: S → G |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000419988 | 1-776 | E3 ubiquitin-protein ligase UHRF1 | |||
Sequence: MWIQVRTMDGKETHRVDSLSKLTKVDELRVKIAELFNVEPERQRLFYRGKQMEDGHTIFDYNVGLNDIVQLLVRQAVAATVLPKDKEAELSDSDSGCGSAQSESDKGSTHGESDVQSAGASGQTDTADLIDPGFGFYKINEFVDARDLNMGAWFEAQIVKVTKTPAEDGGAEDIVYHVKYEDYPENGVVQLRGKDVRPRARTVYQWHQLEPGMIVMVNYNPDDPKERGYWYDAEIQRKRETRTQREVFGKILLGDAGDSLNDCRIMFVTEIYKIEEPGSAEGPGASSDSPLKKGSNGPECKVCKDDPKKNCRVCNCHVCGIKQDPDKQLLCDECDMAFHTYCLNPPLTTIPDDEDWYCPDCRNDASEVVLAGEKLKESKKKAKMASASSSSQRDWGKGMACVGRTKQCTIVPSNHYGPVPGVPVGTLWKFRVQVSESGVHRPHVAGIHGRSNDGAYSLVLAGGYEDDVDDGNEFTYTGSGGRDLSGNKRTAEQSCDQKLTNMNRALALNCNAAVNDKEGAEAKDWKAGKPVRVVRSSKGRKHSKYSPEDGNRYDGIYKVVKYWPEKGKSGFLVWRYLLKRNDEESAPWTRDGKERIKKLGLTMQYPEGYLEAVAAKEKEKENKNEDDIEETPTKGKRKRKSQSMEEKSSPTKGTPKKMKVEAYKLSKEQKALIKDDELNKKLWDEAMESLSLGPRFVNKVEEVFLCICCQEVVYQPITTECQHNVCRECLQRSFKAKVYTCPACRHDLGKNYQMAVNKPLQAILTQLFPGYSSGRC | ||||||
Modified residue | 649 | Phosphoserine; by CDK2 | ||||
Sequence: S |
Post-translational modification
Phosphorylation at Ser-649 is required for gastrulation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in proliferating tissues. Highly expressed 24-48 hours after fertilization (hpf) in rapidly proliferating tissues, including the tectum, retina and brachial arches. Preferentially expressed in the liver bud and expression is maintained in the fully developed liver. Also expressed in the proximal gut. In adult, the highest expression is detected in testis.
Gene expression databases
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias, zinc finger.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-78 | Ubiquitin-like | ||||
Sequence: MWIQVRTMDGKETHRVDSLSKLTKVDELRVKIAELFNVEPERQRLFYRGKQMEDGHTIFDYNVGLNDIVQLLVRQAVA | ||||||
Region | 88-126 | Disordered | ||||
Sequence: AELSDSDSGCGSAQSESDKGSTHGESDVQSAGASGQTDT | ||||||
Compositional bias | 94-124 | Polar residues | ||||
Sequence: DSGCGSAQSESDKGSTHGESDVQSAGASGQT | ||||||
Region | 135-201 | Tudor-like 1 | ||||
Sequence: GFYKINEFVDARDLNMGAWFEAQIVKVTKTPAEDGGAEDIVYHVKYEDYPENGVVQLRGKDVRPRAR | ||||||
Region | 208-277 | Tudor-like 2 | ||||
Sequence: QLEPGMIVMVNYNPDDPKERGYWYDAEIQRKRETRTQREVFGKILLGDAGDSLNDCRIMFVTEIYKIEEP | ||||||
Region | 278-298 | Disordered | ||||
Sequence: GSAEGPGASSDSPLKKGSNGP | ||||||
Region | 290-299 | Linker | ||||
Sequence: PLKKGSNGPE | ||||||
Zinc finger | 297-364 | PHD-type | ||||
Sequence: GPECKVCKDDPKKNCRVCNCHVCGIKQDPDKQLLCDECDMAFHTYCLNPPLTTIPDDEDWYCPDCRND | ||||||
Region | 331-335 | Histone H3R2me0 binding | ||||
Sequence: CDECD | ||||||
Region | 351-353 | Histone H3R2me0 binding | ||||
Sequence: PDD | ||||||
Domain | 417-580 | YDG | ||||
Sequence: GPVPGVPVGTLWKFRVQVSESGVHRPHVAGIHGRSNDGAYSLVLAGGYEDDVDDGNEFTYTGSGGRDLSGNKRTAEQSCDQKLTNMNRALALNCNAAVNDKEGAEAKDWKAGKPVRVVRSSKGRKHSKYSPEDGNRYDGIYKVVKYWPEKGKSGFLVWRYLLKR | ||||||
Region | 443-444 | Required to promote base flipping | ||||
Sequence: HV | ||||||
Region | 464-467 | Required for formation of a 5-methylcytosine-binding pocket | ||||
Sequence: YEDD | ||||||
Region | 476-479 | Required for formation of a 5-methylcytosine-binding pocket | ||||
Sequence: YTGS | ||||||
Region | 617-660 | Disordered | ||||
Sequence: EKEKENKNEDDIEETPTKGKRKRKSQSMEEKSSPTKGTPKKMKV | ||||||
Zinc finger | 706-745 | RING-type | ||||
Sequence: CICCQEVVYQPITTECQHNVCRECLQRSFKAKVYTCPACR |
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 & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
E7EZF3-1
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
- Length776
- Mass (Da)87,091
- Last updated2011-03-08 v1
- Checksum4B47035A83A6CD76
E7EZF3-2
- Name2
- Differences from canonical
- 293-294: KG → R
Features
Showing features for compositional bias, sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 94-124 | Polar residues | ||||
Sequence: DSGCGSAQSESDKGSTHGESDVQSAGASGQT | ||||||
Sequence conflict | 171-173 | in Ref. 3; AAH58055 | ||||
Sequence: AED → PEE | ||||||
Sequence conflict | 173 | in Ref. 1; AAT68031 | ||||
Sequence: D → S | ||||||
Sequence conflict | 207 | in Ref. 3; AAH58055 | ||||
Sequence: H → R | ||||||
Alternative sequence | VSP_044402 | 293-294 | in isoform 2 | |||
Sequence: KG → R | ||||||
Sequence conflict | 293-294 | in Ref. 1; AAT68031 | ||||
Sequence: KG → SQ | ||||||
Sequence conflict | 537 | in Ref. 1; AAT68031 | ||||
Sequence: S → Y | ||||||
Sequence conflict | 737 | in Ref. 1; AAT68031 and 3; AAH58055 | ||||
Sequence: K → E | ||||||
Sequence conflict | 754 | in Ref. 3; AAH58055 | ||||
Sequence: M → V |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY648713 EMBL· GenBank· DDBJ | AAT68031.1 EMBL· GenBank· DDBJ | mRNA | ||
BX927276 EMBL· GenBank· DDBJ | CAK04045.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FP360035 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC058055 EMBL· GenBank· DDBJ | AAH58055.1 EMBL· GenBank· DDBJ | mRNA |