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NOTCH4 (human)

Overview 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. Note: This description may include information from UniProtKB. Protein type: Membrane protein, integral Cellular Component: nucleoplasm; Golgi membrane; 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; cell fate determination; morphogenesis of a branching structure; activation of Notch receptor target transcription factor; patterning of blood vessels; negative regulation of cell differentiation; embryonic development; mammary gland development; negative regulation of endothelial cell differentiation; hemopoiesis; gene expression; endothelial cell morphogenesis; cell differentiation Reference #:  Q99466 (UniProtKB) Alt. Names/Synonyms: FLJ16302; hNotch4; INT3; MGC74442; Neurogenic locus notch homolog protein 4; NOTC4; Notch 4; Notch 4 extracellular truncation; Notch 4 intracellular domain; Notch homolog 4 (Drosophila); NOTCH3; NOTCH4 Gene Symbols: NOTCH4 Molecular weight: 209,622 Da Basal Isoelectric point: 5.43  Predict pI for various phosphorylation states CST Pathways:  ESC Pluripotency and Differentiation  |  Notch Signaling Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below NOTCH4

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	Modification Sites and Domains	Show Modification Legend
Click here to view phosphorylation modifications only

	Modification Sites in Parent Protein, Orthologs, and Isoforms	Show Modification Legend

SS  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.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human
0	1		S378-p	IDRVGSFsCLCPPGR
0	1		K1735	GARDKWGKTALHWAA
0	1		-	gap

	mouse
S375	IDRVGSFSCLCPPGR
K1730-a	GARDKRGkTALHWAA
T1830-p	EARAHARtTPGGGAA

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