Coatomer subunit alpha (COPA)

Coatomer subunit alpha (COPA) is a core component of the coatomer complex I (COPI), a multi-protein complex essential for retrograde vesicular trafficking from the Golgi apparatus to the endoplasmic reticulum (ER) in eukaryotic cells[1][4][5]. COPA helps mediate intracellular protein sorting, Golgi structure, and maintenance of normal secretory pathway function. The COPA gene also gives rise to xenin, a gastrointestinal peptide hormone that regulates exocrine pancreatic secretion and intestinal motility[1][4][5]. Pathogenic mutations in COPA are linked to COPA syndrome, a rare disorder featuring autoimmunity, autoinflammation, and type I interferonopathy due to aberrant activation of the cGAS/STING signaling pathway[3]. Therapeutic intervention in COPA syndrome has included JAK1/2 inhibitors and experimental STING pathway inhibitors such as H-151[3]. Beyond inherited immune disorders, abnormal COPA transcript editing is implicated in certain cancers such as hepatocellular carcinoma[5]. COPA interacts within the COPI complex with other coatomer subunits (e.g., COPE, COPB1), and defects in related COPI proteins can cause additional developmental or immune pathologies[1][3]. No small-molecule drugs directly targeting COPA are clinically approved; current therapeutic approaches act on downstream pathways dysregulated as a consequence of COPA loss of function.

Other names

Coat protein complex I subunit alphaAlpha-COPHEP-COPCoatomer protein complex subunit alphaCOPI coat complex subunit alphaAlpha coat proteinProxeninXenin

Inhibition of inflammatory signaling (cGAS/STING pathway blockade), JAK-STAT pathway blockade (modulation of IFN signaling)