Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-threonine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-3-O-ubiquitinyl-L-threonine (overall reaction)
(1a) [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [RCR-type E3 ubiquitin transferase]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [RCR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine
(1b) [RCR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-threonine = [RCR-type E3 ubiquitin transferase]-L-cysteine + [acceptor protein]-3-O-ubiquitinyl-L-threonine
Glossary: RCR = RING-Cys-Relay
RING = Really Interesting New Gene
Other name(s): MYCBP2; PHR1
Systematic name: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:acceptor protein ubiquitin transferase (isopeptide bond-forming; RCR-type)
Comments: RCR-type E3 ubiquitin transferases is a class of RING-type E3 ubiquitin transferase (see EC 2.3.2.27) that mediates ubiquitylation of acceptor proteins via an internal cysteine residue. The RING1 domain binds an EC 2.3.2.23, E2 ubiquitin-conjugating enzyme, and transfers the ubiquitin that is bound to it to an internal cysteine residue on a mediator loop of the RCR-type ligase. The ubiquitin may be transferred to a second internal cysteine before the transfer of the ubiquitin from the RCR-type ligase to the substrate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Pao, K.C., Wood, N.T., Knebel, A., Rafie, K., Stanley, M., Mabbitt, P.D., Sundaramoorthy, R., Hofmann, K., van Aalten, D.MF. and Virdee, S. Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity. Nature 556 (2018) 381-385. [PMID: 29643511]