EC - E1 NEDD8-activating enzyme

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IntEnz Enzyme Nomenclature


Accepted name:
E1 NEDD8-activating enzyme
Other name:
NEDD-activating enzyme E1
Systematic name:
[NEDD8 protein]:[E1 NEDD8-activating enzyme] ligase (AMP-forming)



Some RING-type E3 ubiquitin transferase (EC 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, E2 NEDD8-conjugating enzyme, and is eventually conjugated to a lysine residue of specific substrates in the presence of the appropriate E3 transferase (EC, cullin-RING-type E3 NEDD8 transferase).

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB
UniProtKB/Swiss-Prot: (15) [show] [UniProt]


  1. Osaka, F., Kawasaki, H., Aida, N., Saeki, M., Chiba, T., Kawashima, S., Tanaka, K., Kato, S.
    A new NEDD8-ligating system for cullin-4A.
    Genes Dev. 12 : 2263-2268 (1998). [PMID: 9694792]
  2. Gong, L., Yeh, E. T.
    Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway.
    J. Biol. Chem. 274 : 12036-12042 (1999). [PMID: 10207026]

[EC created 2020]