E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of PCNP. May participate in methylation-dependent transcriptional regulation. Important for G1/S transition. Overexpression causes G1 phase cell arrest.
Function:
E3 ubiquitin-protein ligase that is an intermolecular hub protein in the cell cycle network. Through cooperative DNA and histone binding, may contribute to a tighter epigenetic control of gene expression in differentiated cells. Ubiquitinates cyclins, CCND1 and CCNE1, in an apparently phosphorylation-independent manner and induces G1 arrest. Also ubiquitinates PCNP leading to its degradation by the proteasome. E3 SUMO-, but not ubiquitin-, protein ligase for ZNF131.
Subunit:
Homodimer; disulfide-linked. Binds methylated CpG containing oligonucleotides. Interacts with H3: the interaction has a preference for the 'Lys-9' trimethylated form of H3 (H3K9me3). Interacts with PCNP, HDAC1 and CDK2 (inactive form). Component of a complex at least composed of UHRF2, CDK2 and CCNE1. Interacts directly with CCNE1; the interaction ubiquitinates CCNE1 and appears independent of CCNE1 phosphorylation. Interacts with CCND1; the interaction ubiquitinates CCND1 and appears independent of CCND1 phosphorylation. Interacts with p53/TP53 and RB1. Interacts with UBE2I.
Subcellular Location:
Nucleus. Note=Enriched at pericentric heterochromatin (PH). This localization is dependent on the interaction with H3K9me3.
Post-translational modifications:
May be autoubiquitinated; which may lead to proteasomal degradation.
Phosphorylated. Phosphorylation may be mediated by CDK2.
Autosumoylated.
DISEASE:
Note=Associated with various cancers. DNA copy number loss is found in multiple kinds of malignancies originating from the brain, breast, stomach, kidney, hematopoietic tissue and lung.
Similarity:
Contains 1 PHD-type zinc finger.
Contains 1 RING-type zinc finger.
Contains 1 ubiquitin-like domain.
Contains 1 YDG domain.
SWISS:
Q96PU4
Gene ID:
115426
Database links:
Entrez Gene: 115426 Human
Entrez Gene: 109113 Mouse
Entrez Gene: 309331 Rat
SwissProt: Q96PU4 Human
SwissProt: Q7TMI3 Mouse
Unigene: 493401 Human
Unigene: 313364 Mouse
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