NOTCH3

NOTCH3, also known as IMF2, LMNS, CASIL, CADASIL, CADASIL1, is the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. It is a cell surface protein that is ubiquitously expressed in both fetal and adult tissues. NOTCH3 is synthesized in endoplasmic reticulum and maturated via extensive proteolytic cleavage in the trans-Golgi network before transported to cell surface, where it serves as a receptor for membrane-bound ligands Jagged1, Jagged2, and Delta1. NOTCH3 is involved in the regulation of cell-fate and its expression level affects cell differentiation, proliferation, and apoptosis.

NOTCH3 is a phosphorylated membrane protein that contains a total number of 5 ankyrin (ANK) repeats, 34 epidermal growth factor (EGF)-like domains, and 3 LNR (Lin/Notch) repeats. Mutations in NOTCH3 has been reported to cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Abnormally elevated expression of NOTCH3 is also associated with several types of cancer, including breast, lung, and ovarian cancers. Currently, NOTCH3 is considered as a good candidate for cancer treatment and many immunotherapies, including ADC, are being actively explored.

Entrez Gene ID: 4854
UniProt ID: Q9UM47