COP9 signalosome complex subunit 5

COPS5 (COP9 signalosome complex subunit 5) is a probable protease subunit of the COP9 signalosome (CSN), a regulatory complex that mediates deneddylation of cullin subunits in SCF-type E3 ligase complexes, thereby reducing their ubiquitin-conjugation activity (UniProt: Q92905). The CSN complex also participates in phosphorylation of key signaling proteins including p53, c-jun, and IκBα, processes essential for controlling protein degradation and cell stress responses.

COPS5 operates broadly across cellular and developmental pathways through its role in the ubiquitin-proteasome system. The protein interacts directly with numerous CSN-regulated substrates and promotes proteasomal degradation of proteins like BRSK2, positioning it as a central node in proteostatic control (UniProt: Q92905).

COPS5 shows elevated levels in Alzheimer's disease brain tissue, with a mean log2 fold-change of +0.74 relative to age-matched controls in post-mortem samples analyzed by quantitative proteomics across multiple subcellular fractions (Chaparral AD proteomics). This upregulation may reflect altered proteostatic regulation or compensatory changes in the ubiquitin-proteasome system in AD pathology.