PSMD14

26S proteasome non-ATPase regulatory subunit 14, also known as 26S proteasome non-ATPase subunit Rpn11, is an is_associated_with::enzyme that in humans is encoded by the PSMD14 is_associated_with::gene. This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex. Nine subunits Rpn3, Rpn5, Rpn6, Rpn7, Rpn8, Rpn9, Rpn11, is_associated_with::SEM1(Yeast analogue for human protein is_associated_with::DSS1), and Rpn12 form the lid sub complex of 19S regulatory particle for is_associated_with::proteasome complex.

Gene
The gene PSMD14 encodes one of 26S proteasome non-ATPase subunit. The human gene PSMD14 has 12 Exons and locates at chromosome band 2q24.2.

Protein
The human protein 26S proteasome non-ATPase regulatory subunit 14 is 34.6 kDa in size and composed of 310 amino acids. The calculated theoretical pI of this protein is 6.06.

Complex assembly
26S is_associated_with::proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory particles (RP, or 19S proteasome) on either one side or both side of the barrel-shaped 20S. The CP and RPs pertain distinct structural characteristics and biological functions. In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin-like activities. These proteolytic active sites located in the inner side of a chamber formed by 4 stacked rings of 20S subunits, preventing random protein-enzyme encounter and uncontrolled protein degradation. The 19S regulatory particles can recognize ubiquitin-labeled protein as degradation substrate, unfold the protein to linear, open the gate of 20S core particle, and guide the substate into the proteolytic chamber. To meet such functional complexity, 19S regulatory particle contains at least 18 constitutive subunits. These subunits can be categorized into two classes based on the ATP dependence of subunits, ATP-dependent subunits and ATP-independent subunits. According to the protein interaction and topological characteristics of this multisubunit complex, the 19S regulatory particle is composed of a base and a lid subcomplex. The base consists of a ring of six AAA ATPases (Subunit Rpt1-6, systematic nomenclature) and four non-ATPase subunits (Rpn1, Rpn2, Rpn10, and Rpn13).s The lid sub complex of 19S regulatory particle consisted of 9 subunits. The assembly of 19S lid is independent to the assembly process of 19S base. Two assembly modules, Rpn5-Rpn6-Rpn8-Rpn9-Rpn11 modules and Rpn3-Rpn7-SEM1 modules were identified during 19S lid assembly using yeast proteasome as a model complex. The subunit Rpn12 incorporated into 19S regulatory particle when 19S lid and base bind together. Among these lid subunits, protein Rpn11 presents the metalloproteases activity to hydrolyze the is_associated_with::ubiquitin molecules from the poly-ubiquitin chain before protein substrates are unfolded and degraded. During substrate degradation, the 19S regulatory particles undergo a conformation switch that is characterized by a rearranged ATPase ring with uniform subunit interfaces. Notably, Rpn11 migrates from an occluded position to directly above the central pore, thus facilitating substrate deubiquitination concomitant with translocation.

Function
As the degradation machinery that is responsible for ~70% of intracellular proteolysis, proteasome complex (26S proteasome) plays a critical roles in maintaining the homeostasis of cellular proteome. Accordingly, misfolded proteins and damaged protein need to be continuously removed to recycle amino acids for new synthesis; in parallel, some key regulatory proteins fulfill their biological functions via selective degradation; furthermore, proteins are digested into peptides for MHC class I antigen presentation. To meet such complicated demands in biological process via spatial and temporal proteolysis, protein substrates have to be recognized, recruited, and eventually hydrolyzed in a well controlled fashion. Thus, 19S regulatory particle pertains a series of important capabilities to address these functional challenges. To recognize protein as designated substrate, 19S complex has subunits that are capable to recognize proteins with a special degradative tag, the ubiquitinylation. It also have subunits that can bind with nucleotides (e.g., ATPs) in order to facilitate the association between 19S and 20S particles, as well as to cause confirmation changes of alpha subunit C-terminals that form the substate entrance of 20S complex. Protein Rpn11 presents the metalloproteases activity to hydrolyze the is_associated_with::ubiquitin molecules from the poly-ubiquitin chain before protein substrates are unfolded and degraded