lnx1

LNX1, short for ligand of numb protein X 1, is a member of the LNX family of multi-domain E3 ubiquitin ligases encoded by the LNX1 gene in humans. The protein is characterized by the presence of multiple PDZ domains and a RING finger domain, which together mediate protein-protein interactions and catalytic ubiquitination of substrates. Alternative splicing gives rise to several transcript variants, and the LNX1 protein can be found in different cellular compartments depending on cellular context and interacting partners.

LNX1 functions as an E3 ubiquitin ligase, tagging selected substrates with ubiquitin. A primary substrate is NUMB, a cytoplasmic adaptor protein that negatively regulates Notch signaling. Through PDZ-mediated binding to NUMB, LNX1 can ubiquitinate NUMB, promoting its degradation or endosomal trafficking. This modulation of NUMB levels or localization can influence Notch pathway activity and, by extension, processes such as cell fate determination during development and neuronal differentiation.

Expression studies in model organisms and human tissues show LNX1 is broadly expressed, with evidence for enriched expression in neural tissues during development. The precise roles of LNX1 in human biology are still being defined, and its activity may intersect with other signaling networks beyond Notch. In disease contexts, altered LNX1 expression or dysregulation of its ubiquitin ligase activity has been investigated in research on cancer and neurodevelopment, but robust clinical associations remain to be established.

Overall, LNX1 is a conserved, multi-domain E3 ubiquitin ligase that links PDZ-mediated binding to targeted ubiquitination, most notably of NUMB, thereby contributing to the regulation of Notch signaling and related cellular decisions.