UHRF2 Protein, Human

UHRF2, an E3 ubiquitin ligase, plays pivotal roles in orchestrating DNA methylation, histone modifications, cell cycle progression, and DNA repair processes. As a specific reader for 5-hydroxymethylcytosine (5hmC), UHRF2 recruits various substrates to these genomic sites, facilitating their ubiquitination and ensuring the maintenance of 5mC levels at specific loci, thereby regulating neuron-related gene expression. In the realm of cell cycle regulation, UHRF2 exerts control by ubiquitinating cyclins CCND1 and CCNE1, leading to G1 arrest. It also targets PCNP for ubiquitin-mediated degradation by the proteasome. Functioning as a key player in DNA damage response, UHRF2 ubiquitinates p21/CDKN1A, promoting its proteasomal degradation and actively participating in DNA repair. Acting as an interstrand cross-links (ICLs) sensor, UHRF2 collaborates with UHRF1 to recruit FANCD2 to ICLs, resulting in FANCD2 monoubiquitination and subsequent activation. Furthermore, UHRF2 contributes to the UV-induced DNA damage response by physically interacting with ATR upon irradiation, thereby facilitating ATR activation.