Ubiquitin-activating enzyme E3

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Ubiquitin-activating enzyme E3, alongside E1 and E2 enzymes and ATP, is required for the addition of at least 5 ubiquitin molecules, to form a chain, to protein substrates. Such substrates attach to a 26S proteasome to be then converted into amino acids or used for antigen presentation. Ubiquitination, and therefore ubiquitin-activating enzyme E3, is required for the activation of NF-kB, a nuclear factor if the kappa light chain in B cell antibodies, which is utilised in responses to stress and infection

The E3 enzyme is a ligase and works via mediating the attachment of ubiquitin molecules, previously attached to the E2 enzymes to the target protein[1].

There are many families of the ubiquitin ligase in which the mechanisms of attaching ubiquitin differ. Enzymes of the HECT domain type require an additional transthiolation reaction, one previously in order to remove E1 from ubiquitin and add E2 in replacement. Contrastingly, ligases of the RING finger-type have the ability to remove ubiquitin from E2 onto protein substrates in one step[2].


  1. Annual Review of Biochemistry (1998) (67: 425-479) "The ubiquitin system" Hershko A, Ciechanover A. https://www.annualreviews.org/doi/10.1146/annurev.biochem.67.1.425
  2. Metzger MB, Hristova VA, Weissman AM (Feb 2012). HECT and RING finger families of E3 ubiquitin ligases at a glance. Journal of Cell Science. 125 (Pt 3): 531–7. doi:10.1242/jcs.091777
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