PSMD7

26S proteasome non-ATPase regulatory subunit 7, also known as 26S proteasome non-ATPase subunit Rpn8,is an is_associated_with::enzyme that in humans is encoded by the PSMD7 is_associated_with::gene.

The 26S proteasome is a multicatalytic is_associated_with::proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 is_associated_with::ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. is_associated_with::Proteasomes are distributed throughout is_associated_with::eukaryotic cells at a high concentration and cleave peptides in an ATP/is_associated_with::ubiquitin-dependent process in a non-is_associated_with::lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of is_associated_with::class I MHC peptides.

Gene
The gene PSMD7 encodes a non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 17. The human gene PSMD7 has 7 Exons and locates at chromosome band 16q22.3.

Protein
The human protein 26S proteasome non-ATPase regulatory subunit 14 is 37 kDa in size and composed of 324 amino acids. The calculated theoretical pI of this protein is 6.11.

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. Recent evidence of crystal structures of proteasomes isolated from Saccharomyces cerevisiae suggests that the catalytically active subunit Rpn8 and subunit Rpn11 form heterodimer. The data also reveals the details of the Rpn11 active site and the mode of interaction with other subunits.

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.