NOTCH precursor cleaved to form mature NOTCH

Stable Identifier
R-HSA-1912369
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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The NOTCH receptor is synthesized as a precursor polypeptide (approx. 300 kDa) associated with the endoplasmic reticulum membrane. The mature NOTCH receptor is produced by proteolytic cleavage to form a heterodimer. The enzyme responsible is a furin-like convertase which cleaves the full-length precursor into a transmembrane fragment (NTM) of approximate size 110 kDa and an extracellular fragment (NEC) of approximate size 180 kDa. The mature NOTCH receptor is reassembled as a heterodimer (Blaumueller et al. 1997, Logeat et al. 1998). Both disulfide bonds and calcium-mediated ionic interactions stabilize the heterodimer (Rand et al. 2000, Gordon et al. 2009). This process takes place in the trans-Golgi network . Mammalian NOTCH is predominantly presented as a heterodimer on the cell surface. Although FURIN-mediated cleavage is evolutionarily conserved, it may not be mandatory for Drosophila Notch function (Kidd et al. 2002).

Literature References
PubMed ID Title Journal Year
19701457 Effects of S1 cleavage on the structure, surface export, and signaling activity of human Notch1 and Notch2

Gordon, WR, Vardar-Ulu, D, L'Heureux, S, Ashworth, T, Malecki, MJ, Sanchez-Irizarry, C, McArthur, DG, Histen, G, Mitchell, JL, Aster, JC, Blacklow, SC

PLoS One 2009
9653148 The Notch1 receptor is cleaved constitutively by a furin-like convertase

Logeat, F, LeBail, O, Jarriault, S, Seidah, NG

Proc Natl Acad Sci U S A 1998
12049766 Furin cleavage is not a requirement for Drosophila Notch function

Kidd, S, Lieber, T

Mech Dev 2002
9727485 Roles for proteolysis and trafficking in notch maturation and signal transduction

Chan, YM, Jan, YN

Cell 1998
10669757 Calcium depletion dissociates and activates heterodimeric notch receptors

Rand, MD, Grimm, LM, Artavanis-Tsakonas, S, Patriub, V, Blacklow, SC, Sklar, J

Mol Cell Biol 2000
9244302 Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane

Blaumueller, CM, Qi, H, Zagouras, P, Artavanis-Tsakonas, S

Cell 1997
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
serine-type endopeptidase activity of FURIN [Golgi membrane]
Physical Entity
Activity
Orthologous Events
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Reviewed
Created