Protein: E3 ubiquitin-protein ligase UHRF1 (EC 2.3.2.27) (Nuclear protein 95) (Nuclear zinc finger protein Np95) (RING-type E3 ubiquitin transferase UHRF1) (Ubiquitin-like PHD and RING finger domain-containing protein 1) (mUhrf1) (Ubiquitin-like-containing PHD and RING finger domains protein 1) (Q8VDF2)
Organism: Mus musculus (Mouse)
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 such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. Plays a role in DNA repair by cooperating with UHRF1 to ensure recruitment of FANCD2 to interstrand cross-links (ICLs) leading to FANCD2 activation ().
Subcellular location: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00358, ECO:0000269|PubMed:10984098, ECO:0000269|PubMed:11161719, ECO:0000269|PubMed:14993289, ECO:0000269|PubMed:17994007, ECO:0000269|PubMed:21489993, ECO:0000269|PubMed:36056023, ECO:0000269|PubMed:8634372}. Note=Associated, through the YDG domain (also called SRA domain), with replicating DNA from early to late S phase, including at replicating pericentric heterochromatin (PubMed:36056023). Also localizes to euchromatic regions. In non-S-phase cells, homogenously distributed through the nucleus (PubMed:36056023). {ECO:0000269|PubMed:36056023}.
Interaction partners:
- DNA
- Histone-lysine N-methyltransferase EHMT2
- Histone deacetylase 1
- Ubiquitin carboxyl-terminal hydrolase 7
- Histone H3.3
- DNA
- DNA ligase 1
- Histone H3.2
- Histone H3.1
- DNA
Sequence:
MWIQVRTMDGKETHTVNSLSRLTKVQELRKKIEEVFHVEPQLQRLFYRGKQMEDGHTLFDYDVRLNDTIQLLVRQSLALPLSTKERDSELSDSDSGYGVGHSESDKSSTHGEGAAEADDKTVWEDTDLGLYKVNEYVDVRDNIFGAWFEAQVVQVQKRALSEDEPCSSSAVKTSEDDIMYHVKYDDYPEHGVDIVKAKNVRARARTVIPWENLEVGQVVMANYNVDYPRKRGFWYDVEICRKRQTRTARELYGNIRLLNDSQLNNCRIMFVDEVLMIELPKERRPLIASPSQPPPALRNTGKSGPSCRFCKDDENKPCRKCACHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVPPEPEWYCPSCRTDSSEVVQAGEKLKESKKKAKMASATSSSRRDWGKGMACVGRTTECTIVPANHFGPIPGVPVGTMWRFRVQVSESGVHRPHVAGIHGRSNDGAYSLVLAGGYEDDVDNGNYFTYTGSGGRDLSGNKRTAGQSSDQKLTNNNRALALNCHSPINEKGAEAEDWRQGKPVRVVRNMKGGKHSKYAPAEGNRYDGIYKVVKYWPERGKSGFLVWRYLLRRDDTEPEPWTREGKDRTRQLGLTMQYPEGYLEALANKEKSRKRPAKALEQGPSSSKTGKSKQKSTGPTLSSPRASKKSKLEPYTLSEQQANLIKEDKGNAKLWDDVLTSLQDGPYQIFLSKVKEAFQCICCQELVFRPVTTVCQHNVCKDCLDRSFRAQVFSCPACRFELDHSSPTRVNQPLQTILNQLFPGYGSGR