NP95/UHRF1 was originally identified as ICBP90 (inverted CCAAT box-binding protein of 90 kDa) in a one-hybrid screen for proteins that bind the topoisomerase IIalpha gene promoter. NP95/UHRF1 is a heterochromatin binding protein that directly interacts with histones and has proposed roles in the DNA damage response, heterochromatin formation, and cell replication. Structurally, NP95/UHRF1 contains an ubiquitin-like domain (NIRF_N), a plant homeodomain (PHD), a SRA domain, and a RING domain. The RING domain imparts ubiquitin E3 ligase activity that is histone-specific. This E3 ligase activity is proposed to be important to tumor growth. NP95/UHRF1 expression begins in the G1/S phase and continues through mitosis. It has been shown to be required for entry from G1/G0 as well as the G1/S transition in some cell types. NP95/UHRF1 has been found to be part of the pericentric heterochromatin duplication body (pHDB) and involved in the replication and formation of heterochromatin.