Fig. 1

An overview of proposed NOTCH4 structure and signaling. a The receptor NOTCH4 is a 2002-amino acid transmembrane protein with its N terminus situated extracellularly (Type I membrane protein). From N terminus to C terminus it consists of 36 epidermal growth factor (EGF) repeats; 3 NOTCH domains (LNR, Lin-12/Notch repeat); a heterodimerization domain (HD) containing the NODP domain; a transmembrane domain (TM); and an intracellular domain. The intracellular domain is made up of ankyrin repeats (ANK) and a PEST domain. b The mechanism of NOTCH family signaling involves binding by a ligand of the DSL family (e.g., DLL4), which results in cleavage of the intracellular domain at the plasma membrane. The intracellular domain translocates to the nucleus where it binds DNA-binding transcription factor RBP-Jk and acts as a transcriptional activator of effector gene transcription such as HES1 and HEY1