NOTCH3-ligand complex is cleaved to produce NEXT3

Stable Identifier
R-HSA-9013284
Type
Reaction [transition]
Species
Homo sapiens
Compartment
extracellular region, plasma membrane
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NOTCH3-ligand complex is cleaved to produce NEXT3
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Ligand binding induces a conformational change in NOTCH3, probably through mechanical pulling of NOTCH3 triggered by endocytosis of the receptor-attached ubiquitinated ligand. This conformational change exposes the S2 site in the extracellular region of NOTCH3 and triggers cleavage of NOTCH3 by ADAM10 metalloprotease, generating the membrane-anchored NOTCH3 fragment NEXT3 (Groot et al. 2014). The extracellular NOTCH3 portion remains attached to the ligand presented on the plasma membrane of a neighboring cell.

Literature References
PubMed ID Title Journal Year
24842903 Regulated proteolysis of NOTCH2 and NOTCH3 receptors by ADAM10 and presenilins

Groot, AJ, Habets, R, Yahyanejad, S, Hodin, CM, Reiss, K, Saftig, P, Theys, J, Vooijs, M

Mol. Cell. Biol. 2014
Participants
Input
Output
Participant Of
hasEvent
Event Information
Go Biological Process
Notch receptor processing, ligand-dependent (0035333)
Catalyst Activity
Catalyst Activity
Title
metallopeptidase activity of ADAM10:Zn2+ [plasma membrane]
Physical Entity
ADAM10:Zn2+ [plasma membrane]
Activity
metallopeptidase activity (0008237)
Orthologous Events
NOTCH3-ligand complex is cleaved to produce NEXT3 (Bos taurus)
NOTCH3-ligand complex is cleaved to produce NEXT3 (Mus musculus)
NOTCH3-ligand complex is cleaved to produce NEXT3 (Rattus norvegicus)
NOTCH3-ligand complex is cleaved to produce NEXT3 (Xenopus tropicalis)
Authored
Orlic-Milacic, M  (2017-09-20)
Reviewed
Haw, R  (2017-10-30)
Created
Orlic-Milacic, M  (2017-07-24)