Notch2 N-Terminal Like Protein (NOTCH2NL)

N2N

SPN	I355
HGNC	31862
PubMed	24140581
UniProt	Q7Z3S9

N2N is a 36-kDa protein distributed throughout the cell and secreted. Its amino-terminal sequence consists of several EGF repeats identical to those of the extracellular region of Notch2, and its carboxyl terminus contains a unique 24-residue domain required for interaction with neutrophil elastase. Neutrophil elastase cleaves N2N within EGF repeats in vitro and in living cells, but the C-terminal domain retards proteolysis.

In vitro, N2N represses transcriptional activities of Notch proteins. Disease-causing mutations of neutrophil elastase disrupt the interaction with N2N, impair proteolysis of N2N and Notch2, and interfere with Notch2 signaling, suggesting defective proteolysis of an inhibitory form of Notch as an explanation for the alternate switching of cell fates characteristic of hereditary neutropenia.

Reference

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Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"A novel notch protein, N2N, targeted by neutrophil elastase and implicated in hereditary neutropenia."
Mol. Cell. Biol. 24:58-70(2004) [PubMed] [Europe PMC] [Abstract]