NEDD8

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Neural precursor cell expressed, developmentally down-regulated 8
Protein NEDD8 PDB 1ndd.png
PDB rendering based on 1ndd.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols NEDD8 ; NEDD-8
External IDs OMIM603171 MGI97301 HomoloGene4485 GeneCards: NEDD8 Gene
RNA expression pattern
PBB GE NEDD8 201840 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4738 18002
Ensembl ENSG00000129559 ENSMUSG00000010376
UniProt Q15843 P29595
RefSeq (mRNA) NM_006156 NM_008683
RefSeq (protein) NP_006147 NP_032709
Location (UCSC) Chr 14:
24.22 – 24.23 Mb
Chr 14:
55.66 – 55.67 Mb
PubMed search [1] [2]

NEDD8 is a protein that in humans is encoded by the NEDD8 gene.[1][2] (In Saccharomyces cerevisiae this protein is known as Rub1.) This ubiquitin-like protein (ULP), which becomes covalently conjugated to a limited number of cellular proteins in a manner analogous to ubiquitination. Human NEDD8 shares 60% amino acid sequence identity to ubiquitin. The most substrates of NEDD8 modification are the Cullin subunits of Cullin-based E3 ubiquitin ligases, which are active only when neddylated. Their NEDDylation is critical for the recruitment of E2 to the ligase complex, thus facilitating ubiquitin conjugation. NEDD8 modification has therefore been implicated in cell cycle progression and cytoskeletal regulation.

Activation and conjugation[edit]

As with ubiquitin and SUMO, NEDD8 is conjugated to cellular proteins after its C-terminal tail is processed. The NEDD8 activating E1 enzyme is a heterodimer composed of APPBP1 and UBA3 subunits. The APPBP1/UBA3 enzyme has homology to the N- and C-terminal halves of the ubiquitin E1 enzyme, respectively. The UBA3 subunit contains the catalytic center and activates NEDD8 in an ATP-dependent reaction by forming a high-energy thiolester intermediate. The activated NEDD8 is subsequently transferred to the UbcH12 E2 enzyme, and is then conjugated to specific substrates in the presence of the appropriate E3 ligases.

Removal[edit]

There are several different proteases which can remove NEDD8 from protein conjugates. UCHL1, UCHL3 and USP21 proteases have dual specificity for NEDD8 and ubiquitin. Proteases specific for NEDD8 removal are the COP9 signalosome which removes NEDD8 from the CUL1 subunit of SCF ubiquitin ligases, and NEDP1 (or DEN1, SENP8).[3]

Interactions[edit]

NEDD8 has been shown to interact with:

References[edit]

  1. ^ Kamitani T, Kito K, Nguyen HP, Yeh ET (Nov 1997). "Characterization of NEDD8, a developmentally down-regulated ubiquitin-like protein". The Journal of Biological Chemistry 272 (45): 28557–62. doi:10.1074/jbc.272.45.28557. PMID 9353319. 
  2. ^ "Entrez Gene: NEDD8 neural precursor cell expressed, developmentally down-regulated 8". 
  3. ^ "Boston Biochem NEDD8 Reagents Overview". Archived from the original on 2008-05-02. Retrieved 2008-04-29. 
  4. ^ Antenos M, Casper RF, Brown TJ (Nov 2002). "Interaction with Nedd8, a ubiquitin-like protein, enhances the transcriptional activity of the aryl hydrocarbon receptor". The Journal of Biological Chemistry 277 (46): 44028–34. doi:10.1074/jbc.M202413200. PMID 12215427. 
  5. ^ Hipp MS, Raasi S, Groettrup M, Schmidtke G (Apr 2004). "NEDD8 ultimate buster-1L interacts with the ubiquitin-like protein FAT10 and accelerates its degradation". The Journal of Biological Chemistry 279 (16): 16503–10. doi:10.1074/jbc.M310114200. PMID 14757770. 
  6. ^ Kamitani T, Kito K, Fukuda-Kamitani T, Yeh ET (Dec 2001). "Targeting of NEDD8 and its conjugates for proteasomal degradation by NUB1". The Journal of Biological Chemistry 276 (49): 46655–60. doi:10.1074/jbc.M108636200. PMID 11585840. 
  7. ^ a b Gong L, Yeh ET (Apr 1999). "Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway". The Journal of Biological Chemistry 274 (17): 12036–42. PMID 10207026. 
  8. ^ Wada H, Kito K, Caskey LS, Yeh ET, Kamitani T (Oct 1998). "Cleavage of the C-terminus of NEDD8 by UCH-L3". Biochemical and Biophysical Research Communications 251 (3): 688–92. doi:10.1006/bbrc.1998.9532. PMID 9790970. 

Further reading[edit]