E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. It thereby participates in many processes regulated by the Notch signaling pathway, such as midline cell fate specification prior to germ layer formation, patterning of sensory cell differentiation in the ear, neurogenesis of the hindbrain and commitment to a secretory fate in the intestine. Essential for early embryonic development. 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. Interacts with deltaA (dla) and deltaD (dld). Localizes to the plasma membrane. The N-terminal domain (1-440) mediates the interaction with Delta receptors. The ANK repeats are involved in Delta receptor internalization. The RING fingers mediate the E3 ligase activity. The third RING finger probably plays a central role in this process. The role of the other RING fingers remains unclear. Mutants have a disorganized brain and neural tube, bent tail and very small or absent otoliths.