Signal peptide peptidase

The Signal Peptide Peptidase (SPP) and its homologs (SPPL2a/b/c, SPPL3) are a class of transmembrane aspartyl proteases with the conserved motives YD ... GxGD ...PALL. Their sequences are highly conserved in different vertebrate species. Their substrates are Type II transmembrane proteins.

Physiologically SPP processes signal peptides of HLA preproteins. A 9 AS cleavage fragment is then presented on HLA-E receptors and modulates the activity of natural killer cells.

SPP also plays a pathophysiolocigal role; it cleaves the core protein of Hepatitis C virus and thus influences the reproduction rate of HCV.

SPPL2a/b promotes the intramembrane cleavage of TNFα in activated dendritic cells and might play an immunomodulatory role.