NEDD8
Function
Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis via its conjugation to a limited number of cellular proteins, such as cullins or p53/TP53 (PubMed:10318914, PubMed:10597293, PubMed:11953428, PubMed:14690597, PubMed:15242646, PubMed:9694792, PubMed:38605244). Attachment of NEDD8 to cullins is critical for the recruitment of E2 to the cullin-RING-based E3 ubiquitin-protein ligase complex, thus facilitating polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins (PubMed:10318914, PubMed:10597293, PubMed:11953428, PubMed:20688984, PubMed:9694792, PubMed:38605244). Attachment of NEDD8 to p53/TP53 inhibits p53/TP53 transcriptional activity (PubMed:15242646). Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M (PubMed:14690597).
Post-translational modifications
Cleavage of precursor form by UCHL3 or SENP8 is necessary for function.
(Microbial infection) Deamidated at Gln-40 by bacterial cyclomodulin Cif produced by enteropathogenic E.coli, Y.pseudotuberculosis or B.pseudomallei, leading to impair NEDD8 ability to activate cullin-RING-based E3 ubiquitin-protein ligase complexes (CRL complexes) (PubMed:20688984, PubMed:21903097, PubMed:23175788, PubMed:23589306, PubMed:26632597). Deamidation occurs on NEDD8-modified cullins (PubMed:20850415, PubMed:21903097). NEDD8 deamidation prevents switching from the inactive to active state by maintaining the 'closed' structure of the CRL complexes (PubMed:23589306, PubMed:26632597). Deamidation may also impair its deconjugation by the COP9 signalosome; However this result needs additional evidences (PubMed:20850415, PubMed:21903097).
Sequence Similarities
Belongs to the ubiquitin family.
Tissue Specificity
Highly expressed in heart, skeletal muscle, spleen, thymus, prostate, testis, ovary, colon and leukocytes.
Cellular localization
- Nucleus
- Mainly nuclear.
Alternative names
Ubiquitin-like protein NEDD8, Neddylin, Neural precursor cell expressed developmentally down-regulated protein 8, NEDD-8, NEDD8