Human Notch-2 Intracellular Domain Antibody

Human Notch-2 is a 300 kDa type I transmembrane glycoprotein that is one of four human Notch homologues involved in developmental processes (1‑3). Although Notch proteins are structurally and functionally similar, deletion of either Notch-1 or Notch-2 is lethal, showing that not all functions overlap (4, 5). Mice with hypomorphic Notch-2 show defects in the development of kidney, heart and eyes (6). Notch-2 is up‑regulated in mature B cells and is critical for differentiation to splenic marginal zone B cells (7). Notch-2 is also preferentially expressed in choroid plexus epithelia and neuronal precursors (8, 9). Human Notch-2 is synthesized as a 2471 amino acid (aa) precursor that contains a 25 aa signal sequence, a 1652 aa extracellular domain (ECD), and a 794 aa transmembrane (TM) and cytoplasmic segment. The ECD contains 35 EGF-like repeats and three Lin-12/Notch repeats, while the cytoplasmic region shows six ankyrin repeats, a glutamine-rich domain and a PEST sequence. Binding of ligands, including Jagged and Delta-like molecules in humans, has been localized to the 11^th and 12^th EGF-like repeats of Notch (10). Notch receptors undergo post-translational furin-type proteolytic cleavage (11). This forms a heterodimer through the interaction of a hydrophobic area in the ligand‑binding extracellular region with the TM/cytoplasmic portion (11, 12). Upon ligand binding, additional sequential proteolysis by TNF-converting enzyme (ADAM‑17) and the presenilin-dependent gamma -secretase results in the release of the Notch intracellular domain (NICD) which translocates into the nucleus, activating transcription of Notch-responsive genes (13). Human Notch-2 ECD (aa 26‑530) shows 93%, 93%, 96% and 96% aa identity with the corresponding regions of mouse, rat, canine, and bovine Notch-2, respectively. This region also exhibits approximately 60% aa identity with human Notch-1 and Notch-3.