UHRF1 Protein, Human (Active)

UHRF1 is a multidomain protein that functions as a pivotal epigenetic regulator by bridging DNA methylation and chromatin modification. Its YDG domain specifically recognizes hemimethylated DNA at replication forks and recruits DNMT1 methyltransferase to maintain methylation patterns during DNA replication. Additionally, UHRF1's tudor-like regions and PHD-type zinc fingers bind histone H3 trimethylated at Lys-9 (H3K9me3) and unmethylated at Arg-2 (H3R2me0), respectively, recruiting chromatin-associated proteins. Enriched in pericentric heterochromatin, it recruits chromatin modifiers for replication, while in euchromatic regions it potentially suppresses transcription via DNA methylation and histone modifications. UHRF1 exhibits E3 ubiquitin ligase activity targeting proteins like histone H3 and PML, though its in vivo chromatin relationship remains unclear. It collaborates with UHRF2 in DNA repair by facilitating FANCD2 recruitment to interstrand cross-links (ICLs). Recent studies reveal its role in spindle architecture through Lys-63-linked ubiquitination of KIF11, controlling spindle localization.