PSMA3


Description

The PSMA3 (proteasome 20S subunit alpha 3) is a protein-coding gene located on chromosome 14.

Proteasome subunit alpha type-3, also known as macropain subunit C8 and proteasome component C8, is a protein that in humans is encoded by the PSMA3 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.

== Function == The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. As a component of alpha ring, proteasome subunit alpha type-3 contributes to the formation of heptameric alpha rings and substrate entrance gate.

== Structure == The human protein proteasome subunit alpha type-3 is 28.4 kDa in size and composed of 254 amino acids. The calculated theoretical pI of this protein is 5.08.

=== Complex assembly === The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: the two end rings are each formed by 7 alpha subunits, and the two central rings are each formed by 7 beta subunits. Three beta subunits (beta1, beta2, and beta5) each contains a proteolytic active site and has distinct substrate preferences.

PSMA3 is a subunit of the 20S core proteasome, a complex responsible for degrading most intracellular proteins. This complex interacts with various regulatory particles, including two 19S regulatory particles, forming the 26S proteasome. The 26S proteasome degrades ubiquitinated proteins in an ATP-dependent manner, crucial for maintaining protein homeostasis by removing misfolded or damaged proteins. Additionally, the 20S proteasome associates with PA200 or PA28, mediating ubiquitin-independent protein degradation involved in spermatogenesis (20S-PA200) and generating MHC class I-presented antigenic peptides (20S-PA28). PSMA3 directly binds to the C-terminus of CDKN1A, leading to its degradation. Moreover, it negatively regulates the membrane trafficking of the cell-surface thromboxane A2 receptor (TBXA2R) isoform 2.

PSMA3 is also known as HC8, PSC3.

Associated Diseases


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