The p62 protein/sequestosome 1 (SQSTM1) comprises a Phox and Bem1p (PB1) domain at the NH2-terminal, a ZZ type zinc finger domain, a Pro, Glu, Ser, and Thr (PEST) region consisting of putative phosphorylation sites, and a ubiquitin-associated (UBA) domain at the COOH-terminal. The SQSTM1 gene is mapped to the human chromosome location 5q35.3.
The p62 protein/sequestosome 1 (SQSTM1) is a multifunctional protein, which binds to ubiquitin. It acts as a scaffold protein for the nuclear factor kappa-B (NF-ΚB) signaling pathway. SQSTM1 also regulates apoptosis and autophagy. Mutations in this gene lead to sporadic and familial Paget disease of bone. It is also associated with protein aggregation diseases, such as Lewy bodies in Parkinson′s disease, neurofibrillary tangles in Alzheimer′s disease, and huntingtin aggregates. SQSTM1 is commonly found in inclusion bodies containing polyubiquitinated protein aggregates that accumulate in several degenerative diseases. p62 polymerizes through its N-terminal Phox and Bem1p (PB1) domain and interacts with polyubiquitinated proteins through its C-terminal ubiquitin-associated (UBA) domain. p62 acts as a linker between protein aggregates and the autophagy machinery.
