E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications, cell cycle and DNA repair (PubMed:15178429, PubMed:29506131, PubMed:27743347, PubMed:23404503). Acts as a specific reader for 5-hydroxymethylcytosine (5hmC) and thereby recruits various substrates to these sites to ubiquitinate them (PubMed:27129234, PubMed:24813944). This activity also allows the maintenance of 5mC levels at specific genomic loci and regulates neuron-related gene expression (By similarity). Participates in cell cycle regulation by ubiquitinating cyclins CCND1 and CCNE1 and thereby inducing G1 arrest (PubMed:15178429, PubMed:15361834, PubMed:21952639). Ubiquitinates also PCNP leading to its degradation by the proteasome (PubMed:14741369, PubMed:12176013). Plays an active role in DNA damage repair by ubiquitinating p21/CDKN1A leading to its proteosomal degradation (PubMed:29923055). Promotes also DNA repair by acting as an interstrand cross-links (ICLs) sensor. Mechanistically, cooperates with UHRF1 to ensure recruitment of FANCD2 to ICLs, leading to FANCD2 monoubiquitination and subsequent activation (PubMed:30335751). Contributes to UV-induced DNA damage response by physically interacting with ATR in response to irradiation, thereby promoting ATR activation (PubMed:33848395). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. E3 ligase activity is robustly activated by 5-hydroxymethylcytosine. Protein modification; protein ubiquitination. 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) (By similarity). Interacts with PCNP (PubMed:12176013, PubMed:14741369). Interacts with HDAC1 (PubMed:15361834). Interacts directly with CCNE1; the interaction ubiquitinates CCNE1 and appears independent of CCNE1 phosphorylation (PubMed:21952639). Interacts with CCND1; the interaction ubiquitinates CCND1 and appears independent of CCND1 phosphorylation (PubMed:21952639). Interacts with p53/TP53 and RB1 (PubMed:21952639). Interacts with UBE2I (PubMed:23404503). Interacts with ZNF618 (PubMed:27129234). Interacts with UHRF1 (PubMed:30335751). Interacts with FANCD2 (PubMed:30335751). Interacts with ATR (PubMed:33848395). Interacts with PCNA (PubMed:28951215). Enriched at genomic loci that are enriched for 5-hydroxymethylcytosine (5hmC). Up-regulated in proliferating fetal lung fibroblasts and in U-937 myeloid leukemia cells. Down-regulated in these cells by growth arrest and differentiation. In other cell types which cannot leave the cell cycle, such as tumoral HT-1080 and Hep-G2, levels are consistently up-regulated. The YDG domain recognizes and binds 5-hydroxymethylcytosine (5hmC). May be autoubiquitinated; which may lead to proteasomal degradation. Phosphorylated. Phosphorylation may be mediated by CDK2. Autosumoylated. 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.