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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).


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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.


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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 »

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 »

Target Id 3235
Nomenclature S-phase kinase associated protein 2
Previous and unofficial names FBL1 | FBXL1
Genes SKP2 (Hs), Skp2 (Mm), Skp2 (Rn)
Ensembl ID ENSG00000145604 (Hs), ENSMUSG00000054115 (Mm), ENSRNOG00000059059 (Rn)
UniProtKB AC Q13309 (Hs), Q99J53 (Mm)
compound 14i [PMID: 37204466] pIC50 8.6 [25]
Comment Skp2 is a F-box domain-containing protein that acts as a substrate recognition component of cullin-RING E3 ubiquitin ligase complexes. It binds regulatory subunits of cyclin-dependent kinases (CKS1A and CKS1B) that modulate the biological function of cyclin dependent kinases catalytic activity, and are thus involved in regulating G1/S transition in the cell cycle. Skp2 is an oncology drug target.

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

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NC-IUPHAR subcommittee and family contributors

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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.