Alternative titles; symbolsNEDD8-SPECIFIC PROTEASE 1; NEDP1DENEDDYLASE 1; DEN1HGNC Approved Gene Symbol: SENP8Cytogenetic location: 15q23 Genomic coordinates...
Alternative titles; symbols
HGNC Approved Gene Symbol: SENP8
Cytogenetic location: 15q23 Genomic coordinates (GRCh38): 15:72,114,257-72,143,691 (from NCBI)
NEDD8 (603171) is a ubiquitin-like protein that becomes conjugated to the cullin (see CUL1; 603134) 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 (Gan-Erdene et al., 2003).
▼ Cloning and Expression
By searching a database for sequences similar to yeast Ulp1, followed by PCR of a kidney cDNA library, Mendoza et al. (2003) cloned NEDP1. 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.
Wu et al. (2003) purified DEN1 from HeLa cells based on its ability to deneddylate a CUL1 substrate. By searching for sequences similar to a DEN1 tryptic fragment, followed by PCR of a fetal brain cDNA library, they cloned DEN1. Western blot analysis detected the purified protein at an apparent molecular mass of 24 kD.
▼ Gene Function
Mendoza et al. (2003) confirmed that recombinant NEDP1 expressed in bacteria processed the NEDD8 precursor protein after the second gly in the diglycine motif, but it did not process SUMO1 (601912) or ubiquitin (see 191339). NEDP1 showed no activity against full-length SUMO1, SUMO2 (603042), or SUMO3 (602231). Inhibition and mutagenesis studies indicated that NEDP1 is a cysteine protease. NEDP1 deconjugated NEDD8 from CUL2 (603135) in vitro and from modified CUL4A (603137) in vivo.
Wu et al. (2003) determined that recombinant DEN1 bound NEDD8 in an in vitro pull-down assay, but showed much lower binding to SUMO1 and ubiquitin. They showed that DEN1 processed NEDD8 precursor proteins into the mature protein and that DEN1 deconjugated hyperneddylated CUL1.
Gan-Erdene et al. (2003) found that DEN1 catalyzed hydrolysis of a NEDD8 substrate at a much higher rate than it did a ubiquitin substrate. It did not catalyze hydrolysis of a SUMO1 substrate.
The International Radiation Hybrid Mapping Consortium mapped the NEDP1 gene to chromosome 15 (SGC33966).