Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Mainly acts as a positive regulator of Notch, but it also acts as a negative regulator, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Involved in neurogenesis, lymphogenesis and myogenesis, and may also be involved in MZB (Marginal zone B) cell differentiation. Promotes B-cell development at the expense of T-cell development, suggesting that it can antagonize NOTCH1. Functions as an ubiquitin ligase protein in vivo, mediating ubiquitination and promoting degradation of MEKK1, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity. 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. Protein modification; protein ubiquitination. Homodimer. May form a heterodimer with other members of the Deltex family. Interacts with NOTCH1 via its N-terminal region and EIF3F, the interaction is required for NOTCH1 deubiquitination. Interacts with EP300. Forms a heterodimer with BBAP; the heterodimerization leading to an increase of in vitro ubiquitin ligase activity. Interacts with ITCH. Predominantly cytoplasmic. Associates with endocytic vesicles. Partially nuclear. Predominantly expressed in the brain and testis. Weakly expressed in the thymus, spleen and ovary. Predominantly expressed in regions containing post-mitotic differentiating neurons. In the CNS, it is expressed in the developing neural tube starting from 10.5 dpc in the spinal cord and around 11.5 dpc in the telencephalon. Expressed ubiquitously throughout the spinal cord and telencephalon during neurogenesis. Expressed throughout the developing retina from 12.5 to 15.5 dpc. Expressed in the developing thymus. Not expressed in the somite or presomite during somitogenesis. Expressed slightly later that Dtx2. The WWE domains are thought to mediate some protein-protein interaction, and are frequently found in ubiquitin ligases. Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination catalyzed by ITCH. Splicing acceptor site not canonical. Belongs to the Deltex family.