Blood vessel epicardial substance (BVES) also known as popeye domain-containing protein 1 (POPDC1) is a protein that in humans is encoded by the BVES gene. Bves is a highly conserved, transmembrane protein that is involved in cell adhesion, cell motility, and most recently has been shown to play a role in vesicular transport. Bves is found in a wide variety of organisms (from flies to humans) and is a member of the evolutionarily conserved Popdc family of proteins. Although the precise molecular function of Bves is unknown, disruption of this protein results in developmental defects and impaired cellular processes fundamental to living organisms. Discovery Bves was discovered simultaneously by two independent labs in 1999 (Bves was also named Popdc1 at the time of discovery; the current accepted convention is Bves). Although initially isolated from cardiac tissue, it was later revealed that Bves is highly expressed in muscle, epithelial and brain tissue. Most studies have focused on determining the function of Bves in epithelial tissue at the cellular level. Gene family Bves is the most studied member of the Popeye domain containing (Popdc) family of genes. The two other members of this family are Popdc2 and Popdc3. Popdc2 and Popdc3 are only found in higher vertebrates and share 50% of their DNA sequence, whereas Bves is only 25% homologous with the evolutionary younger Popdc family members. All three members of the Popdc family contain the highly conserved Popeye domain as the family was named for this specific protein motif. Structure Bves is a three-pass transmembrane protein with a short extracellular N-terminus (~40aa) and a larger intracellular C-terminus (~250aa). Within the C-terminus is the Popeye domain, which has been postulated to be important for Bves function. The Popeye domain shares no homology with any known protein motifs, and specific function of this domain is currently unknown, although it is highly conserved across species. Bves exists as a homodimer in vivo, and homodimerization has been shown to be important for function. Localization/expression Bves is expressed in muscle, epithelial and brain tissue, and is thus found in many adult organs. During development, Bves is detected in all three germ layers and later localizes to the aforementioned tissues. Subcellular localization is present at the plasma membrane and is also seen in punctate, intracellular vesicles. Bves demonstrates dynamic localization, dependent upon cell-cell junction formation. Prior to cell-cell contact, Bves is localized mostly to intracellular vesicles, but