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B6CHA3 · UHRF1_XENLA

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

  • 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.

Type
IDPosition(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 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 Processheterochromatin formation
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
    • Nuclear zinc finger protein Np95 (XNp95)
    • 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
    • Synonyms
      np95

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Amphibia > Batrachia > Anura > Pipoidea > Pipidae > Xenopodinae > Xenopus > Xenopus

Accessions

  • Primary accession
    B6CHA3

Proteomes

Organism-specific databases

Subcellular Location

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

Keywords

Phenotypes & Variants

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004199891-772E3 ubiquitin-protein ligase UHRF1

Expression

Gene expression databases

    • 432234Expressed in egg cell and 19 other cell types or tissues

Interaction

Protein-protein interaction databases

Structure

Family & Domains

Features

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

Type
IDPosition(s)Description
Domain1-77Ubiquitin-like
Region90-111Disordered
Region129-205Tudor-like 1
Region212-281Tudor-like 2
Region291-299Linker
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
Compositional bias615-644Basic and acidic residues
Region615-649Disordered
Zinc finger703-742RING-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

  • Sequence status
    Complete
  • Length
    772
  • Mass (Da)
    86,974
  • Last updated
    2008-11-25 v1
  • MD5 Checksum
    6CC29C07318681782C4328EF079FA2E0
MWIQVRTMDGRDTRRIDSLSKLTKVDDLRDRIQQLFGVALESQRLFYRGKQMENGHTLFDYSVGLNDIVQLLVRQIPDSFPTKHKECELSDASAGCGSGQRDSDSGSGEGAMDVDGQSISIIGENVGTSLYKKNDLVDARDLNMGAWFEAQIVNVSKKVGPYGTLPEVSDTSVTSDAIIYHVKYEDYPENGVVQLTCKDVRLRARTTLPWHEIKVGQVVMVNYNPDEPKERGYWYDAEILRKHESKKIKEIYAKVLLGDAGDSLNDCRIRFVNEIYKIEEPGSTYLNTESPQKRQNGPECKHCKDNPKRACRMCACCICGGKQDPEKQLLCDECDLAFHIYCLKPPLSVIPQDEDWYCPDCRNDASEVVLAGEKLKESKKKARMASANSSSQRDWGKGMACVGRSRECTIVPSNHYGPIPGVPVGTLWKFRVQVSESGVHRPHVAGIHGRSNDGSYSLVLAGGYEDDVDNGNEFTYTGSGGRDLSGNKRTAEQSCDQKLSNMNRALALNCSAPINDKEGSIAKDWRAGKPVRVVRNSKGRKHSKYAPEEGNRYDGIYKVVKYWPEKGKSGFLVWRYLLRRDDYEPAPWSKEGKERIKKLGLTMQYPDGYLETLASKEREKENKTEDEPIDSPSKGKRKRNSDNEQTAAKSIPKKMKVASYKLTLEQKTLIKQDVLNAKLWSEVMLFLKEGPKFVNKVEETFLCICCQEVVYEPVTTECHHNICKGCLDRSFKALVHSCPACRHDLGKNYPLNVNKPLQAILSQLFPGYESGR

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias615-644Basic and acidic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
EU177101
EMBL· GenBank· DDBJ
ABY28114.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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