Ubiquitin-conjugating enzyme E2 W (UBE2W)

Ubiquitin-conjugating enzyme E2 W (UBE2W) is an E2 class enzyme essential for the ubiquitination system, which labels target proteins with ubiquitin for subsequent cellular processes such as degradation, trafficking, or regulation. Uniquely among E2 enzymes, UBE2W is specialized to catalyze the monoubiquitination of protein N-termini rather than the typical lysine side chains, influencing the fate or function of specific substrates involved in DNA repair (e.g., Fanconi anemia proteins) and protein quality control (such as the E3 ligase CHIP). Altered function or expression of UBE2W has been implicated in neurodegenerative diseases such as Charcot-Marie-Tooth disease and Machado-Joseph disease, and may influence cellular sensitivity to DNA-damaging agents. UBE2W works in coordination with E1 and E3 ligases (notably with E3 ligase FANCL in DNA repair), and its activity may prime substrates for further polyubiquitination or biological modifications. Its action is also relevant for cellular protein homeostasis and the response to proteotoxic or genotoxic stress.

Other names

UBC16UBC-16E2 ubiquitin-conjugating enzyme WN-terminal E2 ubiquitin-conjugating enzymeN-terminus-conjugating E2Ubiquitin carrier protein WUbiquitin-conjugating enzyme 16Ubiquitin-protein ligase WFLJ11011

Drugs targeting UBE2W would likely act via inhibition or modulation of its ubiquitin-conjugating enzymatic activity, altering substrate ubiquitination, and thereby protein stability or cellular signaling.