Activating the ubiquitin family: UBA6 challenges the field

Trends Biochem Sci. 2008 May;33(5):230-7. doi: 10.1016/j.tibs.2008.01.005. Epub 2008 Mar 18.


Since its discovery in 1981, ubiquitin-activating enzyme 1 was thought to be the only E1-type enzyme responsible for ubiquitin activation. Recently, a relatively uncharacterized E1 enzyme, designated ubiquitin-like modifier activating enzyme 6, was also shown to activate ubiquitin. Ubiquitin-activating enzyme 1 and ubiquitin-like modifier activating enzyme 6 are both essential proteins, and each uses a different spectrum of ubiquitin-conjugating (E2) enzymes. Ubiquitin-like modifier activating enzyme 6 activates not only ubiquitin, but also the ubiquitin-like modifier FAT10 (human leukocyte antigen F-associated transcript 10), which, similarly to ubiquitin, serves as a signal for proteasomal degradation. This new layer of regulation in ubiquitin activation markedly increases the versatility of the ubiquitin conjugation system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Evolution, Molecular
  • Humans
  • Models, Molecular
  • Saccharomyces cerevisiae / enzymology
  • Ubiquitin-Activating Enzymes / genetics
  • Ubiquitin-Activating Enzymes / metabolism
  • Ubiquitins / genetics
  • Ubiquitins / physiology*


  • UBA6 protein, human
  • UBD protein, human
  • Ubiquitins
  • Ubiquitin-Activating Enzymes