Protein zyg-11 homolog B

ZYG11B (protein zyg-11 homolog B) is a substrate adapter subunit of the E3 ubiquitin ligase complex ZYG11B-CUL2-Elongin BC that targets proteins bearing N-terminal degrons for proteasomal degradation (UniProt: Q9C0D3). The protein recognizes substrates with N-terminal glycine, serine, alanine, or cysteine residues and plays roles in clearing caspase-cleaved proteolytic fragments during apoptosis, quality control of N-myristoylation, and amplification of cGAS to enhance innate immune responses.

ZYG11B operates in ubiquitin-proteasome and innate immune pathways across multiple cellular compartments. UniProt curators report no direct disease association; however, the protein's involvement in protein quality control and immune regulation suggests potential relevance to neuroinflammatory processes.

ZYG11B is downregulated in Alzheimer's disease brain tissue (Chaparral AD proteomics), with a mean log2 fold-change of −0.84 compared to age-matched controls in post-mortem human brain analyzed by TMT-labeled quantitative proteomics. This reduced expression may reflect impaired protein quality control or altered immune response dynamics in the AD brain.