Popeye domain-containing protein 2 (POPDC2)

Popeye domain-containing protein 2 (POPDC2) is a transmembrane protein predominantly expressed in cardiac and skeletal muscle, belonging to the Popeye (POP) gene family, which also includes POPDC1 and POPDC3[1][2][4]. It contains three transmembrane domains and a cytoplasmic Popeye domain, which binds cyclic AMP (cAMP) with high affinity and mediates cAMP-dependent signaling[2][6]. POPDC2 plays a critical role in maintaining normal heart rhythm by regulating heart rate dynamics, primarily through modulating the surface expression and function of the two-pore domain potassium channel TREK-1, thereby influencing cardiac pacemaking and conduction[1][2][6]. Mutations or loss of function in POPDC2 cause stress-dependent bradyarrhythmia and inherited arrhythmia both in animal models and human disease, and are also associated with limb-girdle muscular dystrophy type 2X[1][2][4]. POPDC2 may interact with additional cAMP pathway proteins (e.g., PDE4, adenylyl cyclase 9), indicating a broader role in cyclic nucleotide signaling beyond ion channel regulation[4][6]. No approved drugs currently target POPDC2 directly, but its function highlights potential relevance for arrhythmia and muscle disease research and therapy.

Other names

Popeye domain cAMP effector 2POP2Popeye protein 2popeye domain containing 2

Modulates potassium channel (TREK-1) surface expression and current density via cAMP binding; functions as a cAMP effector protein relevant to signaling pathways in cardiac and skeletal muscle[1][2][6]