New kids on the block: The Popeye domain containing (POPDC) protein family acting as a novel class of cAMP effector proteins in striated muscle

Cell Signal. 2017 Dec;40:156-165. doi: 10.1016/j.cellsig.2017.09.015. Epub 2017 Sep 20.


The cyclic 3',5'-adenosine monophosphate (cAMP) signalling pathway constitutes an ancient signal transduction pathway present in prokaryotes and eukaryotes. Previously, it was thought that in eukaryotes three effector proteins mediate cAMP signalling, namely protein kinase A (PKA), exchange factor directly activated by cAMP (EPAC) and the cyclic-nucleotide gated channels. However, recently a novel family of cAMP effector proteins emerged and was termed the Popeye domain containing (POPDC) family, which consists of three members POPDC1, POPDC2 and POPDC3. POPDC proteins are transmembrane proteins, which are abundantly present in striated and smooth muscle cells. POPDC proteins bind cAMP with high affinity comparable to PKA. Presently, their biochemical activity is poorly understood. However, mutational analysis in animal models as well as the disease phenotype observed in patients carrying missense mutations suggests that POPDC proteins are acting by modulating membrane trafficking of interacting proteins. In this review, we will describe the current knowledge about this gene family and also outline the apparent gaps in our understanding of their role in cAMP signalling and beyond.

Keywords: Atrioventricular block; Heart disease; Limb-girdle muscular dystrophy; Popeye domain containing; Protein interaction; Stress-induced bradycardia; cAMP signalling.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / genetics*
  • Cyclic AMP / genetics*
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Humans
  • Membrane Proteins / genetics*
  • Multigene Family / genetics
  • Muscle Proteins / genetics*
  • Muscle, Striated / growth & development
  • Muscle, Striated / metabolism
  • Protein Domains / genetics
  • Signal Transduction / genetics


  • BVES protein, human
  • Cell Adhesion Molecules
  • Membrane Proteins
  • Muscle Proteins
  • POPDC2 protein, human
  • POPDC3 protein, human
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases