Top ▲

E3 ubiquitin ligase components C

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).

Overview

Click here for help

« Hide

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.

Enzymes

3233
Click here for help

Cbl proto-oncogene B Show summary »

cereblon C Show summary » More detailed page go icon to follow link

DDB1 and CUL4 associated factor 1 Show summary »

F-box protein 3 Show summary »


Target Id 3233
Nomenclature F-box protein 3
Genes FBXO3 (Hs), Fbxo3 (Mm), Fbxo3 (Rn)
Ensembl ID ENSMUSG00000027180 (Mm), ENSRNOG00000009549 (Rn), ENSG00000110429
UniProtKB AC Q9UK99 (Hs), Q9DC63 (Mm), D4ABP9 (Rn)
Inhibitors
BC-1215 pIC50 5.6 [6]
Comment F-box protein 3 is one of the components of the SCF (Skp, Cullin, F-box containing) complex, which is a multi-protein E3 ubiquitin ligase complex that catalyses the ubiquitination of proteins to direct them for proteasomal degradation. Structurally F-box protein 3 contains an F-box domain and an ApaG motif in its C-terminal domain. It is involved in pathways that regulate pro-inflammatory cytokine release, and is a molecular target for anti-inflammatory drug development.

kelch domain containing 2 Show summary »

MDM2 proto-oncogene Show summary » More detailed page go icon to follow link

S-phase kinase associated protein 2 Show summary »

STIP1 homology and U-box containing protein 1 Show summary » More detailed page go icon to follow link

von Hippel-Lindau tumor suppressor Show summary »

zinc finger and BTB domain containing 25 Show summary »

Further reading

Click here for help

Show »

References

Click here for help

Show »

NC-IUPHAR subcommittee and family contributors

Show »

How to cite this family page

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.