UHRF1 Antibody (Center) Blocking Peptide

This gene encodes a member of a subfamily of RING-finger type E3 ubiquitin ligases. The protein binds to specific DNA sequences, and recruits a histone deacetylase to regulate gene expression. Its expression peaks at late G1 phase and continues during G2 and M phases of the cell cycle. It plays a major role in the G1/S transition by regulating topoisomerase IIalpha and retinoblastoma gene expression, and functions in the p53-dependent DNA damage checkpoint. It is regarded as a hub protein for the integration of epigenetic information. This gene is up-regulated in various cancers, and it is therefore considered to be a therapeutic target. Multiple transcript variants encoding different isoforms have been found for this gene. A related pseudogene exists on chromosome 12. [provided by RefSeq, Feb 2014]

UHRF1: 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.

Protein type: DNA-binding; Ligase; Ubiquitin conjugating system; Ubiquitin ligase; EC 6.3.2.-; EC 6.3.2.19; Transcription factor

Chromosomal Location of Human Ortholog: 19p13.3

Cellular Component: euchromatin; heterochromatin; nuclear chromatin; nuclear heterochromatin; nuclear matrix; nucleus; replication fork

Molecular Function: histone binding; identical protein binding; methyl-CpG binding; methylated histone residue binding; nucleosomal histone binding; protein binding; transcription factor activity; ubiquitin-protein ligase activity; zinc ion binding

Biological Process: cell proliferation; histone monoubiquitination; histone ubiquitination; maintenance of DNA methylation; negative regulation of transcription from RNA polymerase II promoter; positive regulation of cellular protein metabolic process; positive regulation of transcription from RNA polymerase II promoter; protein autoubiquitination; protein ubiquitination during ubiquitin-dependent protein catabolic process