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. Note: This description may include information from UniProtKB.
Protein type: Motility/polarity/chemotaxis; Transcription factor; Receptor, misc.; Membrane protein, integral
Cellular Component: Golgi membrane; nucleoplasm; endoplasmic reticulum membrane; acrosome; integral to membrane; plasma membrane; extracellular region; nucleus
Molecular Function: enzyme inhibitor activity; protein binding; enzyme binding; receptor activity; calcium ion binding; transcription factor activity
Biological Process: heart development; positive regulation of transcription, DNA-dependent; positive regulation of JAK-STAT cascade; response to lipopolysaccharide; negative regulation of transcription from RNA polymerase II promoter; cell differentiation in spinal cord; negative regulation of neurogenesis; response to corticosteroid stimulus; negative regulation of BMP signaling pathway; positive regulation of endothelial cell differentiation; astrocyte differentiation; regulation of transcription, DNA-dependent; tissue regeneration; positive regulation of cell proliferation; cardiac muscle morphogensis; negative regulation of ossification; oligodendrocyte differentiation; negative regulation of osteoblast differentiation; heart looping; positive regulation of BMP signaling pathway; mesenchymal cell development; positive regulation of cardiac muscle cell proliferation; positive regulation of astrocyte differentiation; positive regulation of neuroblast proliferation; transcription initiation from RNA polymerase II promoter; organ regeneration; Notch signaling pathway; Notch receptor processing; activation of Notch receptor target transcription factor; negative regulation of oligodendrocyte differentiation; negative regulation of neuron differentiation; response to muramyl dipeptide; negative regulation of catalytic activity; epithelial to mesenchymal transition; spermatogenesis; gene expression; immune response; positive regulation of transcription from RNA polymerase II promoter; negative regulation of myoblast differentiation; determination of left/right symmetry; negative regulation of transcription, DNA-dependent; positive regulation of cell migration
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.