Transferases;
Acyltransferases;
Aminoacyltransferases
BRITE hierarchy

[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine:[cullin] [NEDD8-protein] transferase (isopeptide bond-forming; RING-type)

[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin]-L-lysine = [E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin]-N6-[NEDD8-protein]-yl-L-lysine

[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine;
[cullin]-L-lysine

Some RING-type E3 ubiquitin transferase (EC 2.3.2.27) are not able to bind a substrate protein directly. Instead, they form a complex with a cullin scaffold protein and a substrate recognition module, which is named CRL for Cullin-RING-Ligase. The cullin protein needs to be activated by the ubiquitin-like protein NEDD8 in a process known as neddylation. The transfer of NEDD8 from a NEDD8-specific E2 enzyme onto the cullin protein is a secondary function of the RING-type E3 ubiquitin transferase in the CRL complex. The process requires auxiliary factors that belong to the DCN1 (defective in cullin neddylation 1) family.

EC 2.3.2.32 created 2017

1  [PMID:18826954]

Kim AY, Bommelje CC, Lee BE, Yonekawa Y, Choi L, Morris LG, Huang G, Kaufman A, Ryan RJ, Hao B, Ramanathan Y, Singh B

SCCRO (DCUN1D1) is an essential component of the E3 complex for neddylation.

J Biol Chem 283:33211-20 (2008)
DOI:10.1074/jbc.M804440200

2  [PMID:18206966]

Kurz T, Chou YC, Willems AR, Meyer-Schaller N, Hecht ML, Tyers M, Peter M, Sicheri F

Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation.

Mol Cell 29:23-35 (2008)
DOI:10.1016/j.molcel.2007.12.012

3  [PMID:20832729]

Scott DC, Monda JK, Grace CR, Duda DM, Kriwacki RW, Kurz T, Schulman BA

A dual E3 mechanism for Rub1 ligation to Cdc53.

Mol Cell 39:784-96 (2010)
DOI:10.1016/j.molcel.2010.08.030

4  [PMID:24949976]

Scott DC, Sviderskiy VO, Monda JK, Lydeard JR, Cho SE, Harper JW, Schulman BA

Structure of a RING E3 trapped in action reveals ligation mechanism for the ubiquitin-like protein NEDD8.

Cell 157:1671-84 (2014)
DOI:10.1016/j.cell.2014.04.037

5  [PMID:23201271]

Monda JK, Scott DC, Miller DJ, Lydeard J, King D, Harper JW, Bennett EJ, Schulman BA

Structural conservation of distinctive N-terminal acetylation-dependent interactions across a family of mammalian NEDD8 ligation enzymes.

Structure 21:42-53 (2013)
DOI:10.1016/j.str.2012.10.013