19S

19S refers to the regulatory particle of the 26S proteasome, a large protein complex responsible for ATP-dependent degradation of ubiquitinated proteins in eukaryotic cells. Positioned at one end of the 20S core particle, the 19S regulatory particle recognizes polyubiquitinated substrates, removes some ubiquitin chains, unfolds the substrates, and translocates them into the proteolytic core for destruction. This process is essential for protein quality control, regulation of cellular processes, and maintenance of protein homeostasis.

The 19S particle is structured into two subcomplexes: a base and a lid. The base contains six AAA+ ATPase subunits (Rpt1–Rpt6) that form an ATPase ring driving substrate unfolding and gate opening of the 20S core, along with non-ATPase subunits such as Rpn1 and Rpn2 that help dock substrates. The lid comprises several non-ATPase subunits, including Rpn3, Rpn5, Rpn6, Rpn7, Rpn9, Rpn11 (a deubiquitinase that trims ubiquitin chains), and Rpn12. Receptors Rpn10 and Rpn13 recognize ubiquitin tags, and Sem1 acts as an accessory component influencing certain lid functions.

Functionally, the 19S particle coordinates recognition of ubiquitinated proteins, deubiquitination, substrate unfolding, and translocation into the 20S core. Its activity is regulated to ensure selective degradation and proper cellular responses to stress, growth signals, and developmental cues. Disruption of 19S subunits can impair proteasome function and protein homeostasis, with implications for aging and disease. Inhibitors targeting the 26S proteasome, including drugs that affect 19S activity, are used clinically in certain cancer therapies. See also proteasome and ubiquitin–proteasome system.