Coatomer subunit alpha

Coatomer subunit alpha (COPA) is a core component of the coatomer complex, a cytosolic protein assembly that mediates retrograde and biosynthetic transport between the endoplasmic reticulum and Golgi apparatus (UniProt: P53621). The complex binds to dilysine motifs on transport vesicles and is recruited to membranes by ADP-ribosylation factors; it plays essential roles in Golgi structural integrity and LDL receptor recycling. COPA has also been characterized as xenin, which influences gastrointestinal secretion and motility through neurotensin receptor signaling.

COPA is associated with autoinflammation and autoimmunity, systemic, with immune dysregulation (AIAISD; MIM 616414), an autosomal dominant condition featuring inflammatory arthritis, interstitial lung disease, and renal involvement (UniProt: P53621).

In Alzheimer's disease, COPA is significantly down-regulated in post-mortem AD brain tissue relative to age-matched controls (mean log2FC −0.1552; Chaparral AD proteomics). This down-regulation was observed in human brain tissue analyzed via tandem mass spectrometry across subcellular fractions, suggesting reduced coatomer-dependent vesicular trafficking in the diseased brain.