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. May be involved in DNA repair. Defects in UHRF1 may be a cause of cancers. Overexpressed in many different forms of human cancers, including bladder, breast, cervical, colorectal and prostate cancers, as well as pancreatic adenocarcinomas, rhabdomyosarcomas and gliomas. Plays an important role in the correlation of histone modification and gene silencing in cancer progression. Expression is associated with a poor prognosis in patients with various cancers, suggesting that it participates in cancer progression. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Ubiquitin ligase; EC 6.3.2.-; Ubiquitin conjugating system; EC 184.108.40.206; Ligase; DNA binding protein; Transcription factor
Molecular Function: identical protein binding; protein binding; nucleosomal histone binding; methyl-CpG binding; zinc ion binding; histone binding; ubiquitin-protein ligase activity; transcription factor activity; methylated histone residue binding
Biological Process: histone monoubiquitination; cell proliferation; protein autoubiquitination; maintenance of DNA methylation; transcription, DNA-dependent; positive regulation of cellular protein metabolic process; histone ubiquitination; protein ubiquitination during ubiquitin-dependent protein catabolic process; positive regulation of transcription from RNA polymerase II promoter; negative regulation of transcription from RNA polymerase II promoter; cell cycle; DNA repair
Alt. Names/Synonyms: E3 ubiquitin-protein ligase UHRF1; FLJ21925; hNP95; HuNp95; ICBP90; Inverted CCAAT box-binding protein of 90 kDa; MGC138707; NP95; Nuclear protein 95; Nuclear zinc finger protein Np95; RING finger protein 106; RNF106; Transcription factor ICBP90; Ubiquitin-like PHD and RING finger domain-containing protein 1; ubiquitin-like with PHD and ring finger domains 1; ubiquitin-like, containing PHD and RING finger domains, 1; Ubiquitin-like-containing PHD and RING finger domains protein 1; UHRF1
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.