Sentrin Specific Protease 8 (SENP8)

NEDD8 is a ubiquitin-like protein that becomes conjugated to the cullin subunit of several ubiquitin ligases. This conjugation, called neddylation, is required for optimal ubiquitin ligase activity. NEDD8-specific deneddylases, such as NEDP1, or DEN1, are required to process the NEDD8 propeptide at a C-terminal diglycine motif and to remove NEDD8 from cullins. The deduced 212-amino acid protein contains a cysteine protease domain flanked by short N- and C-terminal extensions. PCR analysis showed wide expression of NEDP1, with highest expression in kidney and pancreas.NEDP1 showed no activity against full-length SUMO1, SUMO2, or SUMO3. Inhibition and mutagenesis studies indicated that NEDP1 is a cysteine protease. NEDP1 deconjugated NEDD8 from CUL2 in vitro and from modified CUL4A in vivo.