| 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],developmental stage:Expressed in fetal thymus, liver and kidney.,domain:The RING finger is required for ubiquitin ligase activity.,domain:The YDG domain mediates the interaction with histone H3.,function:Putative E3 ubiquitin-protein ligase. May participate in methylation-dependent transcriptional regulation. Binds to inverted 5-CCAAT-3 box 2 in the TOP2A promoter, and activates TOP2A expression. Important for G1/S transition. May be involved in DNA repair and chromosomal stability.,induction:Up-regulated in proliferating cells, and down-regulated in quiescent cells. Down-regulated upon adriamycin-induced DNA damage, in a TP53/p53 and CDKN1A-dependent way. Induced by E2F1 transcription factor.,pathway:Protein modification, protein ubiquitination.,PTM:Phosphorylated on serine residues. Phosphorylation may enhance DNA-binding activity.,PTM:Ubiquitinated, which leads to proteasomal degradation. Polyubiquitination may be stimulated by DNA damage.,similarity:Contains 1 PHD-type zinc finger.,similarity:Contains 1 ubiquitin-like domain.,similarity:Contains 1 YDG domain.,similarity:Contains 2 RING-type zinc fingers.,subunit:Interacts with histones H3, H1 and H2B (By similarity). Interacts with HDAC1, but not with HDAC2. Interacts with UHRF1BP1. Binds methylated CpG containing oligonucleotides.,tissue specificity:Expressed in thymus, bone marrow, testis, lung and heart. Overexpressed in breast cancer., |
