EC 22.214.171.124 - E1 NEDD8-activating enzyme
IntEnz Enzyme Nomenclature
- ATP + NEDD8 protein + E1 NEDD8-activating enzyme-L-cysteine = AMP + diphosphate + E1 NEDD8-activating enzyme-S-NEDD8 protein-yl-L-cysteine
Some RING-type E3 ubiquitin transferase (EC 126.96.36.199) 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 188.8.131.52, E2 NEDD8-conjugating enzyme, and is eventually conjugated to a lysine residue of specific substrates in the presence of the appropriate E3 transferase (EC 184.108.40.206, cullin-RING-type E3 NEDD8 transferase).
Links to other databases
A new NEDD8-ligating system for cullin-4A.Genes Dev. 12 : 2263-2268 (1998). [PMID: 9694792]
Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway.J. Biol. Chem. 274 : 12036-12042 (1999). [PMID: 10207026]
[EC 220.127.116.11 created 2020]