CATH Classification

Domain Context

CATH Clusters

Superfamily Zinc/RING finger domain, C3HC4 (zinc finger)
Functional Family E3 ubiquitin-protein ligase RBX1

Enzyme Information

2.3.2.32
Cullin-RING-type E3 NEDD8 transferase.
based on mapping to UniProt P62877
S-[NEDD8-protein]-yl-[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin]- L-lysine = [E2 NEDD8-conjugating enzyme]-L-cysteine + N(6)-[NEDD8- protein]-yl-[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.
2.3.2.27
RING-type E3 ubiquitin transferase.
based on mapping to UniProt P62877
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)- ubiquitinyl-[acceptor protein]-L-lysine.
-!- RING E3 ubiquitin transferases serve as mediators bringing the ubiquitin-charged E2 ubiquitin-conjugating enzyme (EC 2.3.2.23) and an acceptor protein together to enable the direct transfer of ubiquitin through the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the epsilon-amino group of an L-lysine residue of the acceptor protein. -!- Unlike EC 2.3.2.26 the RING-E3 domain does not form a catalytic thioester intermediate with ubiquitin. -!- Many members of the RING-type E3 ubiquitin transferase family are not able to bind a substrate directly, and form a complex with a cullin scaffold protein and a substrate recognition module (the complexes are named CRL for Cullin-RING-Ligase). -!- In these complexes, the RING-type E3 ubiquitin transferase provides an additional function, mediating the transfer of a NEDD8 protein from a dedicated E2 carrier to the cullin protein (see EC 2.3.2.32). -!- Cf. EC 2.3.2.31.

UniProtKB Entries (1)

P62877
RBX1_HUMAN
Homo sapiens
E3 ubiquitin-protein ligase RBX1

PDB Structure

PDB 4F52
External Links
Method X-RAY DIFFRACTION
Organism
Primary Citation
Structure of a Glomulin-RBX1-CUL1 Complex: Inhibition of a RING E3 Ligase through Masking of Its E2-Binding Surface.
Duda, D.M., Olszewski, J.L., Tron, A.E., Hammel, M., Lambert, L.J., Waddell, M.B., Mittag, T., Decaprio, J.A., Schulman, B.A.
Mol.Cell