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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Ubiquitination (a.k.a. ubiquitylation) is a protein post-translational modification that typically requires the sequential action of three enzymes: E1 (ubiquitin-activating enzymes), E2 (ubiquitin-conjugating enzymes), and E3 (ubiquitin ligases) [19]. Ubiquitination of proteins can target them for proteasomal degradation, or modulate cellular processes including cell cycle progression, transcriptional regulation, DNA repair and signal transduction.
E3 ubiquitin ligases, of which there are >600 in humans, are a family of highly heterogeneous proteins and protein complexes that recruit ubiquitin-loaded E2 enzymes to mediate transfer of the ubiquitin molecule from the E2 to protein substrates. Target substrate specificity is determined by a substrate recognition subunit within the E3 complex.
E3 ligases are being exploited as pharmacological targets to facilitate targeted protein degradation (TPD), as an alternative to small molecule inhibitors [2], through the development of proteolysis targeting chimeras (PROTACs) and molecular glues.
Cbl proto-oncogene B Show summary » |
cereblon C Show summary » More detailed page |
DDB1 and CUL4 associated factor 1 Show summary » |
F-box protein 3 Show summary » |
kelch domain containing 2 Show summary » |
MDM2 proto-oncogene Show summary » More detailed page |
S-phase kinase associated protein 2 Show summary » |
STIP1 homology and U-box containing protein 1 Show summary » More detailed page |
von Hippel-Lindau tumor suppressor Show summary » |
zinc finger and BTB domain containing 25 Show summary » |
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.