Anti-Notch 3 Antibody, ECD, clone 2G8 clone 2G8, from rat

Neurogenic locus notch homolog protein 3 (UniProt Q9UM47; also known as Notch 3, Notch homolog 3) is encoded by the NOTCH3 (also known as CASIL, CADASIL, IMF2) gene (Gene ID 4854) in human. Notch 3 is a transmembrane receptor required for arterial differentiation and maturation of vascular smooth muscle cells in small arteries. Notch 3 is initially produced with a signal peptide (a.a. 1-39), the removal of which yields the 2282-amino acid Notch 3 (a.a. 40-2321), which undergoes a constitutive proteolytical cleavage, generating the extracellular fragment (Notch3-ECD; a.a. 40-1628) and the transmembrane/cytosolic (Notch3-TMIC; a.a. 1629-2321) fragment that remain associated at the cell surface to form a heterodimeric receptor. The ECD fragment contains all 34 EGF-like domains and the three Lin/Notch (LNR) repeats, while the extracellular portion of TMIC contains 5 ankyrin repeats. Mutations in the NOTCH3 gene have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Pathogenic mutations predominantly affect cysteine residues within EGF-like repeats of Notch3-ECD, leading to Notch3-ECD multimerization and accumulation in the tunica media of vessel walls.