E7EZF3 · UHRF1_DANRE

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

Catalytic activity

  • S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.
    EC:2.3.2.27 (UniProtKB | ENZYME | Rhea)

Pathway

Protein modification; protein ubiquitination.

Features

Showing features for site, binding site.

TypeIDPosition(s)Description
Site314Histone H3K4me0 binding
Site325Histone H3R2me0 binding
Site328Histone H3R2me0 binding
Binding site461-4625-methylcytosine group (UniProtKB | ChEBI) of DNA (UniProtKB | ChEBI)
Binding site4675-methylcytosine group (UniProtKB | ChEBI) of DNA (UniProtKB | ChEBI)
Site477Required to confer preferential recognition of cytosine over thymine
Site487Required to discriminate between hemimethylated DNA versus symmetrically methylated DNA
Site489Required for affinity and specificity for 5-mCpG sequence

GO annotations

AspectTerm
Cellular Componentchromatin
Cellular Componentcytoplasm
Cellular Componenteuchromatin
Cellular Componentheterochromatin
Cellular Componentnucleus
Cellular Componentreplication fork
Molecular Functionhemi-methylated DNA-binding
Molecular Functionhistone binding
Molecular Functionmethylated histone binding
Molecular Functionubiquitin protein ligase activity
Molecular Functionubiquitin-protein transferase activity
Molecular Functionzinc ion binding
Biological Processanimal organ regeneration
Biological Processheterochromatin formation
Biological Processinflammatory response
Biological Processintestinal epithelial structure maintenance
Biological Processlens development in camera-type eye
Biological Processliver development
Biological Processnegative regulation of gene expression via chromosomal CpG island methylation
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processprotein ubiquitination
Biological Processubiquitin-dependent protein catabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    E3 ubiquitin-protein ligase UHRF1
  • EC number
  • Alternative names
    • RING-type E3 ubiquitin transferase UHRF1
    • Ubiquitin-like PHD and RING finger domain-containing protein 1
    • Ubiquitin-like-containing PHD and RING finger domains protein 1

Gene names

    • Name
      uhrf1

Organism names

  • Taxonomic identifier
  • Strains
    • Tuebingen
    • AB
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Actinopterygii > Neopterygii > Teleostei > Ostariophysi > Cypriniformes > Danionidae > Danioninae > Danio

Accessions

  • Primary accession
    E7EZF3
  • Secondary accessions
    • Q1LUQ1
    • Q6DRP6
    • Q6PEI0

Proteomes

Organism-specific databases

Subcellular Location

Nucleus
Cytoplasm
Note: Localizes to replication foci. Enriched in pericentric heterochromatin. Also localizes to euchromatic regions (By similarity).

Keywords

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.

TypeIDPosition(s)Description
Mutagenesis649Non-phosphorylatable mutant; localizes only in nucleus and is unable to localize in cytoplasm.

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00004199881-776E3 ubiquitin-protein ligase UHRF1
Modified residue649Phosphoserine; by CDK2

Post-translational modification

Phosphorylation at Ser-649 is required for gastrulation.

Keywords

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

Family & Domains

Features

Showing features for domain, region, compositional bias, zinc finger.

TypeIDPosition(s)Description
Domain1-78Ubiquitin-like
Region88-126Disordered
Compositional bias94-124Polar residues
Region135-201Tudor-like 1
Region208-277Tudor-like 2
Region278-298Disordered
Region290-299Linker
Zinc finger297-364PHD-type
Region331-335Histone H3R2me0 binding
Region351-353Histone H3R2me0 binding
Domain417-580YDG
Region443-444Required to promote base flipping
Region464-467Required for formation of a 5-methylcytosine-binding pocket
Region476-479Required for formation of a 5-methylcytosine-binding pocket
Region617-660Disordered
Zinc finger706-745RING-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

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

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.

  • Length
    776
  • Mass (Da)
    87,091
  • Last updated
    2011-03-08 v1
  • Checksum
    4B47035A83A6CD76
MWIQVRTMDGKETHRVDSLSKLTKVDELRVKIAELFNVEPERQRLFYRGKQMEDGHTIFDYNVGLNDIVQLLVRQAVAATVLPKDKEAELSDSDSGCGSAQSESDKGSTHGESDVQSAGASGQTDTADLIDPGFGFYKINEFVDARDLNMGAWFEAQIVKVTKTPAEDGGAEDIVYHVKYEDYPENGVVQLRGKDVRPRARTVYQWHQLEPGMIVMVNYNPDDPKERGYWYDAEIQRKRETRTQREVFGKILLGDAGDSLNDCRIMFVTEIYKIEEPGSAEGPGASSDSPLKKGSNGPECKVCKDDPKKNCRVCNCHVCGIKQDPDKQLLCDECDMAFHTYCLNPPLTTIPDDEDWYCPDCRNDASEVVLAGEKLKESKKKAKMASASSSSQRDWGKGMACVGRTKQCTIVPSNHYGPVPGVPVGTLWKFRVQVSESGVHRPHVAGIHGRSNDGAYSLVLAGGYEDDVDDGNEFTYTGSGGRDLSGNKRTAEQSCDQKLTNMNRALALNCNAAVNDKEGAEAKDWKAGKPVRVVRSSKGRKHSKYSPEDGNRYDGIYKVVKYWPEKGKSGFLVWRYLLKRNDEESAPWTRDGKERIKKLGLTMQYPEGYLEAVAAKEKEKENKNEDDIEETPTKGKRKRKSQSMEEKSSPTKGTPKKMKVEAYKLSKEQKALIKDDELNKKLWDEAMESLSLGPRFVNKVEEVFLCICCQEVVYQPITTECQHNVCRECLQRSFKAKVYTCPACRHDLGKNYQMAVNKPLQAILTQLFPGYSSGRC

E7EZF3-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Features

Showing features for compositional bias, sequence conflict, alternative sequence.

TypeIDPosition(s)Description
Compositional bias94-124Polar residues
Sequence conflict171-173in Ref. 3; AAH58055
Sequence conflict173in Ref. 1; AAT68031
Sequence conflict207in Ref. 3; AAH58055
Alternative sequenceVSP_044402293-294in isoform 2
Sequence conflict293-294in Ref. 1; AAT68031
Sequence conflict537in Ref. 1; AAT68031
Sequence conflict737in Ref. 1; AAT68031 and 3; AAH58055
Sequence conflict754in Ref. 3; AAH58055

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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