Recombinant Human Notch-1 Protein (C09-1610-224)

stem cells and inducing differentiation, especially in the nervous system and lymphoid tissues. Notch can specify binary cell fates; for example, promoting T- over B-cell development from a common precursor. More than 50% of human T-lineage acute lymphoblastic leukemia (T-ALL) have activating mutations of Notch1. Human Notch-1 is synthesized as a 2556 amino acid (aa) precursor that contains an 18 aa signal sequence, a 1718 aa extracellular domain (ECD) with 36 EGF-like repeats and three Lin-12/Notch repeats (LNR), a 23 aa transmembrane (TM) segment and a 785 aa cytoplasmic domain containing six ankyrin repeats, a glutamine-rich domain and a PEST sequence. The 11th and 12th EGF-like repeats bind ligands including Jagged and Delta-like families in humans. O-fucosylation by Fringe family members at a site within this region can inhibit the interaction of Notch with Jagged ligands, thereby promoting Delta-like ligand interactions. Notch-1 receptor undergoes post-translational furin-type proteolytic cleavage, forming a heterodimer through interaction of a hydrophobic area C-terminal to the LNR on the 1647 aa ligand-binding extracellular region with the 891 aa transmembrane/cytoplasmic portion. 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. Human Notch-1 ECD aa 19 - 526, including the first 13 EGF repeats, shows 91% aa identity with corresponding regions of mouse and rat, 89% with canine, and 79% with chicken Notch-1. This region also exhibits 60% aa identity with human Notch-2 and Notch-3. Specification: ActiBioPure™, Bioactive, Carrier Free, ≥80%(SDS-PAGE)