Mouse anti-Human/Mouse/Rat sapiens (Human) UHRF2 Monoclonal Antibody

Function

E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications, cell cycle and DNA repair (PubMed:15178429, PubMed:23404503, PubMed:27743347, PubMed:29506131). Acts as a specific reader for 5-hydroxymethylcytosine (5hmC) and thereby recruits various substrates to these sites to ubiquitinate them (PubMed:24813944, PubMed:27129234). 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). Also ubiquitinates PCNP leading to its degradation by the proteasome (PubMed:12176013, PubMed:14741369). Plays an active role in DNA damage repair by ubiquitinating p21/CDKN1A leading to its proteasomal degradation (PubMed:29923055). 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 (PubMed:30335751). Contributes to UV-induced DNA damage response by physically interacting with ATR in response to irradiation, thereby promoting ATR activation (PubMed:33848395)

Subcellular Location

Nucleus; Chromosome

Disease Association

[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]

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) (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)

Pathway

Protein modification; protein ubiquitination

• Mori T. et al. NIRF, a novel RING finger protein, is involved in cell-cycle regulation. — Biochem. Biophys. Res. Commun. (2002)
• Davenport J.W. et al. LMO2-induced T cell leukemias overexpress a novel gene, Uhr1, containing RING and PHD zinc fingers and an ubiquitin-like domain. (JUN-)
• Humphray S.J. et al. DNA sequence and analysis of human chromosome 9. — Nature (2004)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Bechtel S. et al. The full-ORF clone resource of the German cDNA consortium. — BMC Genomics (2007)
• Li Y. et al. NIRF induces G1 arrest and associates with Cdk2. — Biochem. Biophys. Res. Commun. (2004)
• Mori T. et al. NIRF is a ubiquitin ligase that is capable of ubiquitinating PCNP, a PEST-containing nuclear protein. — FEBS Lett. (2004)
• Unoki M. et al. ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain. — Oncogene (2004)