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UBA domain of sequestosome-1 (SQSTM) and similar proteins SQSTM, also called EBI3-associated protein of 60 kDa (EBIAP /p60), phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa, or ubiquitin-binding protein p62, is a widely expressed multifunctional cytoplasmic protein that is able to noncovalently bind ubiquitin and several signaling proteins, suggesting a regulatory role connected to the ubiquitin-proteasome pathway. It functions as a scaffolding protein that regulates a diverse range of signaling pathways leading to activation of the nuclear factor kappa B (NF-kappaB) family of transcription factors. It also plays a novel role in connecting receptor signals with the endosomal signaling network required for mediating TrkA-induced differentiation. SQSTM contains a PB1 dimerization domain, a tumor necrosis factor receptor-associated factor 6 (TRAF6) binding site, and a C-terminal ubiquitin-associated (UBA) domain that mediates the recognition of polyubiquitin chains and ubiquitylated substrates.
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