Poly(rC)-binding protein 2

Poly(rC)-binding protein 2 (PCBP2) is a single-stranded nucleic acid binding protein that preferentially binds oligodeoxycytidine and poly(rU) sequences (UniProt: Q15366). It functions as a negative regulator of antiviral signaling by acting as an adapter between MAVS and the E3 ubiquitin ligase ITCH, thereby promoting MAVS ubiquitination and degradation. PCBP2 also negatively regulates the cGAS-STING pathway by preventing liquid-like droplet formation required for CGAS activation, and plays roles in erythropoiesis and viral RNA replication during poliovirus infection (UniProt: Q15366).

PCBP2 has no annotations in UniProt for disease associations, though its antiviral regulatory functions suggest potential relevance to neuroinflammatory processes. In Alzheimer's disease post-mortem brain tissue, PCBP2 was consistently up-regulated relative to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of 0.17 across subcellular fractions (P2, P3, S2, S3) measured by TMT-labeled proteomics. This modest elevation may reflect altered antiviral or immune signaling in the AD brain environment.