Sentrin-specific protease 8 (SENP8)
The protein contains 212 amino acids for an estimated molecular weight of 24107 Da.
Protease that catalyzes two essential functions in the NEDD8 pathway: processing of full-length NEDD8 to its mature form and deconjugation of NEDD8 from targeted proteins such as cullins or p53. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs930871 |
The reference OMIM entry for this protein is 608659
Sentrin-specific protease family, member 8; senp8
Nedd8-specific protease 1; nedp1
Deneddylase 1; den1
DESCRIPTION
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
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.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the NEDP1 gene to chromosome 15 (TMAP SGC33966). ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 608659 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed