Notch 1: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. May be important for normal lymphocyte function. In altered form, may contribute to transformation or progression in some T-cell neoplasms. Involved in the maturation of both CD4+ and CD8+ cells in the thymus. May be important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, may function as a receptor for neuronal DNER and may be involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Heterodimer of a C-terminal fragment N(TM) and an N- terminal fragment N(EC) which are probably linked by disulfide bonds. Interacts with DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH1. The activated membrane-bound form interacts with AAK1 which promotes NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and SGK1. Interacts with HIF1AN. HIF1AN negatively regulates the function of notch intracellular domain (NICD), accelerating myogenic differentiation. In fetal tissues most abundant in spleen, brain stem and lung. Also present in most adult tissues where it is found mainly in lymphoid tissues. Belongs to the NOTCH family.
Protein type: Motility/polarity/chemotaxis; Receptor, misc.; Oncoprotein; Transcription factor; Membrane protein, integral
Cellular Component: Golgi apparatus; cell surface; membrane; cell; integral to plasma membrane; cytoplasm; plasma membrane; integral to membrane; acrosome; nucleus; receptor complex
Molecular Function: enzyme inhibitor activity; protein binding; enzyme binding; sequence-specific DNA binding; chromatin DNA binding; metal ion binding; chromatin binding; calcium ion binding; receptor activity; transcription factor activity
Biological Process: neural tube development; negative regulation of calcium ion-dependent exocytosis; positive regulation of apoptosis; positive regulation of transcription, DNA-dependent; multicellular organismal development; heart development; positive regulation of JAK-STAT cascade; positive regulation of glial cell differentiation; regulation of cell migration; negative regulation of BMP signaling pathway; neuron differentiation; compartment specification; positive regulation of endothelial cell differentiation; negative regulation of ossification; somatic stem cell division; negative regulation of osteoblast differentiation; embryonic limb morphogenesis; positive regulation of astrocyte differentiation; positive regulation of cardiac muscle cell proliferation; positive regulation of keratinocyte differentiation; negative regulation of photoreceptor cell differentiation; positive regulation of neuroblast proliferation; cell fate commitment; transcription, DNA-dependent; neuron fate commitment; regulation of transcription from RNA polymerase II promoter; keratinocyte differentiation; negative regulation of neuron differentiation; branching morphogenesis of a tube; regulation of gene expression; response to muramyl dipeptide; positive regulation of transcription from RNA polymerase II promoter; determination of left/right symmetry; negative regulation of transcription, DNA-dependent; anagen; foregut morphogenesis; positive regulation of epithelial cell proliferation; osteoblast fate commitment; endoderm development; transcription from RNA polymerase II promoter; epidermis development; cell fate specification; cardiac muscle cell proliferation; negative regulation of transcription from RNA polymerase II promoter; embryonic hindlimb morphogenesis; regulation of epithelial cell proliferation; negative regulation of neurogenesis; negative regulation of cell proliferation; regulation of neurogenesis; glial cell differentiation; astrocyte differentiation; regulation of transcription, DNA-dependent; positive regulation of cell proliferation; forebrain development; cardiac muscle morphogensis; angiogenesis; heart looping; regulation of somitogenesis; cell differentiation; positive regulation of BMP signaling pathway; regulation of developmental process; mesenchymal cell development; Notch signaling pathway; hair follicle morphogenesis; in utero embryonic development; lumen formation; liver development; humoral immune response; activation of Notch receptor target transcription factor; regulation of cell proliferation; negative regulation of oligodendrocyte differentiation; negative regulation of cell differentiation; inflammatory response to antigenic stimulus; axonogenesis; negative regulation of catalytic activity; epithelial to mesenchymal transition; spermatogenesis; sprouting angiogenesis; negative regulation of myoblast differentiation; auditory receptor cell fate commitment; lung development; positive regulation of cell migration
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