Neurogenic locus Notch protein

UniProtKB accession:  P07207

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UniProtKB description:  Essential signaling protein which has a major role in many developmental processes (PubMed:3935325). Functions as a receptor for membrane-bound ligands Delta and Serrate to regulate cell-fate determination (PubMed:10935637, PubMed:15620650, PubMed:12909620, PubMed:18243100). Upon ligand activation, and releasing from the cell membrane, the Notch intracellular domain (NICD) forms a transcriptional activator complex with Su(H) (Suppressor of hairless) and activates genes of the E(spl) complex (PubMed:7671825). Regulates oogenesis, the differentiation of the ectoderm and the development of the central and peripheral nervous system, eye, wing disk, muscles and segmental appendages such as antennae and legs, through lateral inhibition or induction (PubMed:11719214, PubMed:12369105, PubMed:3935325). Regulates neuroblast self-renewal, identity and proliferation through the regulation of bHLH-O proteins; in larval brains, involved in the maintenance of type II neuroblast self-renewal and identity by suppressing erm expression together with pnt; might also regulate dpn expression through the activation of the transcriptional regulator Su(H) (PubMed:27151950, PubMed:28899667, PubMed:20152183, PubMed:18342578, PubMed:23056424, PubMed:21262215). Targeted for ESCRT-mediated endosomal sequestration and lysosomal degradation by various E3 ubiquitin ligases to regulate the Notch signaling pathway (PubMed:17084358, PubMed:22162134, PubMed:33349255). Can undergo ligand-dependent and non-canonical ligand-independent activation (PubMed:22162134). Ligand-independent activation is dependent on endosome acidification and probably occurs in late endosomes or lysosome (PubMed:23178945). Ectopic ligand-independent activation occurs when disruption of the endolysosomal pathway, particularly of the ESCRT-III complex, prevents sequestration of the receptor in intraluminal vesicles of multivesicular bodies (PubMed:17088062, PubMed:17084357, PubMed:17084358, PubMed:23178945).