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Acts as a specific reader for 5-hydroxymethylcytosine (5hmC) and thereby recruits various substrates to these sites to ubiquitinate them (PubMed:23434322, PubMed:28402695). This activity also allows the maintenance of 5mC levels at specific genomic loci and regulates neuron-related gene expression (PubMed:28115522). Participates in cell cycle regulation by ubiquitinating cyclins CCND1 and CCNE1 and thus inducing G1 arrest. Also ubiquitinates PCNP leading to its degradation by the proteasome. Plays an active role in DNA damage repair by ubiquitinating p21/CDKN1A leading to its proteasomal degradation. Also promotes 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. Contributes to UV-induced DNA damage response by physically interacting with ATR in response to irradiation, thereby promoting ATR activation (By similarity)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"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.","ecNumber":"2.3.2.27"}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96PU4"}],"value":"E3 ligase activity is robustly activated by 5-hydroxy-methylcytosine"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"value":"Protein modification; protein ubiquitination"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96PU4"}],"value":"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. Interacts with HDAC1. 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. Interacts with ZNF618. Interacts with UHRF1. Interacts with FANCD2. Interacts with ATR. Interacts with PCNA (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96PU4"}],"value":"Enriched at genomic loci that are enriched for 5-hydroxy-methylcytosine (5hmC)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00358"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21598301"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96PU4"}],"value":"Chromosome","id":"SL-0468"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q7TMI3-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q7TMI3-2"],"sequenceIds":["VSP_013877","VSP_013878"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q7TMI3-3"],"sequenceIds":["VSP_013876"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28115522"}],"value":"Mostly detected in several tissues, including the thymus, spleen, lung, adrenal gland, and ovary. In addition, found in several tissues in the brain (cerebellum, hippocampus, and cerebral cortex)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21598301"}],"value":"Up-regulated during cell differentiation"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"May be autoubiquitinated; which may lead to proteasomal degradation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Phosphorylated. Phosphorylation may be mediated by CDK2 (By similarity)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Autosumoylated"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28115522"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28402695"}],"value":"Deletion mice are viable, fertile, and grossly normal (PubMed:28115522, PubMed:28402695). However, adult mice develop frequent spontaneous seizures and display abnormal electrical activities in brain (PubMed:28402695). In addition, they display reduced 5-hydroxymethylcytosine (5hmC) in genomic DNA in the brain together with impaired spatial memory acquisition and retention (PubMed:28115522)"}],"commentType":"DISRUPTION PHENOTYPE"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":803,"modifier":"EXACT"}},"description":"E3 ubiquitin-protein ligase UHRF2","featureId":"PRO_0000056148"},{"type":"Domain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":78,"modifier":"EXACT"}},"description":"Ubiquitin-like","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00214"}]},{"type":"Domain","location":{"start":{"value":449,"modifier":"EXACT"},"end":{"value":613,"modifier":"EXACT"}},"description":"YDG","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00358"}]},{"type":"Zinc 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