FAT10 : Activated by UBA6 and Functioning in Protein Degradation.

The ubiquitin-like modifier FAT10 (HLA-F adjacent transcript 10) is the only ubiquitin-like modifier known, which apart from ubiquitin, directly targets proteins to proteasomal degradation. The covalent linkage of ubiquitin or other ubiquitin-like modifiers (ULM) to specific substrates is achieved by adjoining them to target proteins with an enzyme cascade using three enzymes: E1, E2 and E3. The first enzyme activates the ULM, the second enzyme serves a conjugating enzyme and the third enzyme ligates the ULM to its target. More recently, the first enzyme in the FAT10 conjugation machinery was characterized. It turned out that the novel E1 activating enzyme UBA6, which serves as a second E1 for ubiquitin in higher eukaryotes, additionally has the ability to activate FAT10. In this chapter the activation of FAT10 and ubiquitin by UBA6 as well as the role of FAT10 in protein degradation will be discussed.