IUBMB Enzyme Nomenclature


Accepted name: E2 NEDD8-conjugating enzyme

Reaction: [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine = [E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine

Glossary: NEDD = Neural-precursor-cell Expressed Developmentally Down-regulated protein

Other name(s): NEDD8-carrier-protein E2; NEDD8-conjugating enzyme E2; UBE2M (gene name); UBE2F (gene name)

Systematic name: [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine:[E2 NEDD8-conjugating enzyme] [NEDD8-protein]-yl transferase

Comments: Some RING-type E3 ubiquitin transferases (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. EC, 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 an 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: BRENDA, EXPASY, KEGG, MetaCyc, PDB, 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]

3. Huang, D.T., Miller, D.W., Mathew, R., Cassell, R., Holton, J.M., Roussel, M.F. and Schulman, B.A. A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8. Nat. Struct. Mol. Biol. 11 (2004) 927-935. [PMID: 15361859]

4. Huang, D.T., Ayrault, O., Hunt, H.W., Taherbhoy, A.M., Duda, D.M., Scott, D.C., Borg, L.A., Neale, G., Murray, P.J., Roussel, M.F. and Schulman, B.A. E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol. Cell 33 (2009) 483-495. [PMID: 19250909]

[EC created 2020]

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