NOTCH4

This gene encodes a member of the NOTCH family of proteins. Members of this Type I transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple different domain types. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor may play a role in vascular, renal and hepatic development. Mutations in this gene may be associated with schizophrenia. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

Full Name

Notch 4

Function

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 (By similarity).

Biological Process

Branching involved in blood vessel morphogenesisISS:UniProtKB
Cell differentiation1 PublicationNAS:UniProtKB
Cell fate determinationManual Assertion Based On ExperimentTAS:UniProtKB
Endothelial cell morphogenesisIEA:Ensembl
Epithelial to mesenchymal transitionManual Assertion Based On ExperimentIMP:ARUK-UCL
HemopoiesisManual Assertion Based On ExperimentTAS:UniProtKB
Mammary gland developmentManual Assertion Based On ExperimentIDA:UniProtKB
Morphogenesis of a branching structureISS:UniProtKB
Negative regulation of cell adhesion molecule productionManual Assertion Based On ExperimentIMP:ARUK-UCL
Negative regulation of cell differentiation1 PublicationNAS:UniProtKB
Negative regulation of cell-cell adhesion mediated by cadherinManual Assertion Based On ExperimentIMP:ARUK-UCL
Negative regulation of endothelial cell differentiationISS:UniProtKB
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of transcription of Notch receptor targetManual Assertion Based On ExperimentTAS:BHF-UCL
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentTAS:UniProtKB
Vasculature developmentISS:UniProtKB
Wound healingIEA:Ensembl

Cellular Location

Cell membrane
Notch 4 intracellular domain
Nucleus
Following proteolytical processing NICD is translocated to the nucleus.

Topology

Extracellular: 24-1447
Helical: 1448-1468
Cytoplasmic: 1469-2003

PTM

Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity).
Phosphorylated.