FAT10

The protein consists of two UBL domains in a head-to-tail arrangement and contains a C-terminal di-glycine motif which is critical for covalent conjugation to target proteins. The two UBL domains of FAT10 are 29% and 35% identical to Ub respectively, and both domains also have conserved lysines (K29, K48, K63) found in Ub. The conjugation and deconjugation enzymes responsible for FAT10 have not yet been identified. However, Ub-specific E1 (Uba6) and E2 (Use1) enzymes can activate and form thioester complex with FAT10 in vitro. These enzymes however have a much higher preference for Ub and the physiological relevance of these activities with FAT10 is still under investigation. Proteins conjugated to FAT10 are rapidly degraded by the proteasome. FAT10 binds non-covalently and interacts with NEDD8 ultimate buster-1L (NUB1L) and binds the proteasome via the UBL domain. NUBL is also induced by IFN-yand thus FAT10 may function as an immune-response-inducible form of Ub.