Questions have been raised since the discovery of UBA6 and its significant coexistence with UBE1 in the ubiquitin-proteasome system (UPS). The facts that UBA6 has the dedicated E2 enzyme USE1 and the E1-E2 cascade can activate and transfer both ubiquitin and ubiquitin-like protein FAT10 have attracted a great deal of attention to the regulational mechanisms of the UBA6-USE1 cascade and to how FAT10 and ubiquitin differentiate with each other. This review recapitulates the latest advances in UBA6 and its bispecific UBA6-USE1 pathways for both ubiquitin and FAT10. The intricate networks of UBA6 and its interplays with ubiquitin and FAT10 are briefly reviewed, as are their individual and collective functions in diverse physiological conditions.
Keywords: FAT10; UBA6; USE1; ubiquitin; ubiquitin proteasome system; ubiquitin-like protein.