Popeye domain-containing protein 1 (POPDC1)

Popeye domain-containing protein 1 (POPDC1/BVES) is a transmembrane cAMP effector protein highly expressed in striated muscle and cardiac tissue. It binds cAMP with high affinity and modulates the trafficking and function of other membrane proteins, particularly the TREK-1 potassium channel, influencing muscle cell membrane potential and excitability. Disease-causing mutations in POPDC1 disrupt its membrane localization or cAMP responsiveness, resulting in limb-girdle muscular dystrophy and heart conduction abnormalities. POPDC1 acts as an adaptor/scaffold for adenylyl cyclase 9 (AC9) and affects local cAMP signaling domains, with loss-of-function leading to pathogenic alterations in muscle and cardiac function. It does not currently have direct therapeutic interventions, but its genetic variants are important biomarkers for related channelopathies and muscular dystrophies.

Other names

BVESPOP1Popeye protein 1HBVESCARICKLGMD2XLGMDR25blood vessel epicardial substance

Modulation of cAMP binding alters membrane localization and potassium channel activity in muscle/cardiac cells. Drug-induced changes in cAMP (e.g., with theophylline) disrupt POPDC1 influence on channel trafficking/function.