Ubiquitin-like modifier FAT10 (FAT10)

Ubiquitin-like modifier FAT10 (commonly abbreviated as FAT10 or UBD) is a member of the ubiquitin-like protein family found exclusively in mammals. It consists of two ubiquitin-like domains linked by a flexible linker, and features a C-terminal di-glycine motif critical for covalent attachment to substrate proteins. FAT10 is expressed predominantly in immune tissues and is highly inducible by pro-inflammatory cytokines, but is also frequently overexpressed in several types of cancer. Unlike ubiquitin, FAT10 directly targets substrates for proteasomal degradation, being co-degraded along with its conjugated proteins without the need for deconjugation. The conjugation ("FAT10ylation") requires an E1 activating enzyme (UBA6) and the E2 conjugating enzyme USE1. In colorectal cancer and potentially other malignancies, overexpression of FAT10 facilitates cell proliferation by promoting the degradation of the tumor suppressor p53, linking FAT10 to tumor progression and making it a potential therapeutic target and cancer biomarker. No specific drugs directly targeting FAT10 are currently approved or widely documented.

Other names

Ubiquitin DUBDdiubiquitinubiquitin-like protein FAT10HLA-F adjacent transcript 10

FAT10ylation: Covalent conjugation to substrate proteins, leading to proteasomal degradation independently of ubiquitin