NOTCH4: 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 regulate branching morphogenesis in the developing vascular system. Heterodimer of a C-terminal fragment N(TM) and a N- terminal fragment N(EC) which are probably linked by disulfide bonds. Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH4. Highly expressed in the heart, moderately in the lung and placenta and at low levels in the liver, skeletal muscle, kidney, pancreas, spleen, lymph node, thymus, bone marrow and fetal liver. No expression was seen in adult brain or peripheral blood leukocytes. Belongs to the NOTCH family. 3 isoforms of the human protein are produced by alternative splicing.
Protein type: Membrane protein, integral
Chromosomal Location of Human Ortholog: 6p21.3
Cellular Component: cell surface; cytoplasmic vesicle; cytosol; endoplasmic reticulum membrane; extracellular region; Golgi membrane; integral to plasma membrane; nucleoplasm; nucleus; plasma membrane
Molecular Function: calcium ion binding; Notch binding; protein binding; protein heterodimerization activity; receptor activity
Biological Process: activation of Notch receptor target transcription factor; cell differentiation; cell fate determination; embryonic development; endothelial cell morphogenesis; gene expression; hemopoiesis; mammary gland development; morphogenesis of a branching structure; negative regulation of cell differentiation; negative regulation of endothelial cell differentiation; negative regulation of Notch signaling pathway; Notch receptor processing; Notch signaling pathway; patterning of blood vessels; positive regulation of angiogenesis; positive regulation of transcription, DNA-dependent; regulation of protein localization; transcription initiation from RNA polymerase II promoter
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