Reaction: ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine = AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
Glossary: NEDD = Neural-precursor-cell Expressed Developmentally Down-regulated protein
Other name(s): NEDD-activating enzyme E1; NAE1 (gene name); UBA3 (gene name)
Systematic name: [NEDD8 protein]:[E1 NEDD8-activating enzyme] ligase (AMP-forming)
Comments: Some RING-type E3 ubiquitin transferase (EC 184.108.40.206) are not able to bind a substrate protein directly. Instead, they form complexes with a cullin scaffold protein and a substrate recognition module, which are known as CRL (Cullin-RING-Ligase) complexes. The cullin protein needs to be activated by the ubiquitin-like protein NEDD8 in a process known as neddylation. Like ubiquitin, the NEDD8 protein ends with two glycine residues. The E1 NEDD8-activating enzyme activates NEDD8 in an ATP-dependent reaction by forming a high-energy thioester intermediate between NEDD8 and one of its cysteine residues. The activated NEDD8 is subsequently transferred to a cysteine residue of EC 220.127.116.11, E2 NEDD8-conjugating enzyme, and is eventually conjugated to a lysine residue of specific substrates in the presence of the appropriate E3 transferase (EC 18.104.22.168, cullin-RING-type E3 NEDD8 transferase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
1. Osaka, F., Kawasaki, H., Aida, N., Saeki, M., Chiba, T., Kawashima, S., Tanaka, K. and Kato, S. A new NEDD8-ligating system for cullin-4A. Genes Dev. 12 (1998) 2263-2268. [PMID: 9694792]
2. Gong, L. and Yeh, E.T. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J. Biol. Chem. 274 (1999) 12036-12042. [PMID: 10207026]