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: Golgi membrane; nucleoplasm; endoplasmic reticulum membrane; cell surface; integral to plasma membrane; extracellular region; plasma membrane; cytosol; nucleus
Molecular Function: protein binding; protein heterodimerization activity; calcium ion binding; receptor activity
Biological Process: transcription initiation from RNA polymerase II promoter; Notch signaling pathway; positive regulation of transcription, DNA-dependent; Notch receptor processing; morphogenesis of a branching structure; cell fate determination; activation of Notch receptor target transcription factor; patterning of blood vessels; negative regulation of cell differentiation; embryonic development; negative regulation of endothelial cell differentiation; mammary gland development; hemopoiesis; gene expression; endothelial cell morphogenesis; cell differentiation
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