The free carboxy-terminal intracellular domain (ICD) of a notch family protein, which is a product of regulated intramembrane proteolysis mediated by the gamma-secretase enzyme complex. This protein fragment is involved in transcriptional regulation of target genes.
Synonyms: Neurogenic Locus Notch Homolog Protein Intracellular Domain Notch Intracellular Domain NICD Neurogenic Locus Notch Homolog Protein ICD Notch ICD Notch Receptor Intracellular Domain
Term information
Full-length notch proteins are post-translationally cleaved by furin to produce a disulfide bound, two-chain protein that is expressed on the cell surface. Once a notch ligand binds the extracellular portion, the larger amino-terminal portion is released from the cell surface and the remaining portion of the receptor, termed the Notch extracellular truncated (NEXT) domain is endocytosed. During endocytosis, NEXT is cleaved sequentially by an ADAM family secretase followed by intramembrane cleavage by gamma-secretase, which allows the notch intracellular domain to dissociate from the membrane and translocate into the nucleus.