Blood vessel epicardial substance
Encyclopedia
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.
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.
, 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.
, Bves is detected in all three germ layer
s 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 as cells begin to form associations, Bves is also present at points of cell-cell contact.
, a protein that modulates Rho GTPases
, Rac1
and Cdc42
, which are important for cell motility through modulation of the actin cytoskeleton. Bves also interacts with VAMP3
, a SNARE
protein important for vesicle fusion. Additionally, Bves has been shown to interact with the tight junction protein, ZO1
, although this interaction is most likely via a protein complex, as a direct physical interaction has never been demonstrated.
signaling cascades. Disruption of Bves results in decreased cell speed and increased cell roundness, which are cell processes modulated by the Rho GTPases, Rac1 and Cdc42. Accordingly, Bves disruption results in decreased active Rac1 and Cdc42. Taken together, these data demonstrate that Bves modulates Rho GTPase signaling cascades through interaction with GEFT to affect cell movement and morphology.
, a member of the SNARE
complex that facilitates vesicle fusion. VAMP3 is important for recycling of integrin
s during cell migration and is also necessary for exocytosis of transferrin
. Upon Bves disruption, cell rounding is increased, a phenotype indicative of decreased adhesion and disruption of integrin function. Accordingly, Bves disruption results in impaired integrin recycling, phenocopying the result seen with inhibition of VAMP3. Similarly, disruption of either Bves results in impaired transferrin recycling again, mimicking the result seen with disruption of VAMP3. Thus, Bves is important for VAMP3-mediated vesicular transport underlying cell migration and transferrin recycling.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the BVES gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Bves is a highly conserved, transmembrane protein that is involved in cell adhesion
Cell adhesion
Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...
, cell motility, and most recently has been shown to play a role in vesicular transport
Vesicular transport protein
A vesicular transport protein is a transmembrane or membrane associated protein. It regulates or facilitates the movement by vesicles of the contents of the cell.-Types:Examples include:* Archain* ARFs* Clathrin* Caveolin...
. 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 domainPopeye protein conserved region
Popeye protein conserved region is a family of evolutionarily related proteins.The Popeye family of proteins, is restricted to vertebrates and is preferentially expressed in developing and adult striated muscle. It is represented by a conserved region which includes three potential transmembrane...
containing (Popdc) family of genes. The two other members of this family are Popdc2
POPDC2
Popeye domain-containing protein 2 is a protein that in humans is encoded by the POPDC2 gene.- Function :This gene encodes a member of the POP family of proteins which contain three putative transmembrane domains. This membrane associated protein is predominantly expressed in skeletal and cardiac...
and Popdc3
POPDC3
Popeye domain-containing protein 3 is a protein that in humans is encoded by the POPDC2 gene.- Function :This gene encodes a member of the POP family of proteins which contain three putative transmembrane domains. This membrane associated protein is predominantly expressed in skeletal and cardiac...
. 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 domainPopeye protein conserved region
Popeye protein conserved region is a family of evolutionarily related proteins.The Popeye family of proteins, is restricted to vertebrates and is preferentially expressed in developing and adult striated muscle. It is represented by a conserved region which includes three potential transmembrane...
, 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 developmentDevelopmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
, Bves is detected in all three germ layer
Germ layer
A germ layer, occasionally referred to as a germinal epithelium, is a group of cells, formed during animal embryogenesis. Germ layers are particularly pronounced in the vertebrates; however, all animals more complex than sponges produce two or three primary tissue layers...
s 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 as cells begin to form associations, Bves is also present at points of cell-cell contact.
Interacting proteins
Bves interacts with GEFTGEFT
RAC/CDC42 exchange factor, also known as GEFT, is a human gene.-Further reading:...
, a protein that modulates Rho GTPases
Rho family of GTPases
The Rho family of GTPases is a family of small signaling G protein , and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic organisms including yeasts and some plants...
, Rac1
RAC1
Ras-related C3 botulinum toxin substrate 1 also known as Rac1 is a protein that in humans is encoded by the RAC1 gene. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.- Function :Rac1 is...
and Cdc42
CDC42
Cell division control protein 42 homolog also known as CDC42 is a protein involved in regulation of the cell cycle. In humans, CDC42 is encoded by the CDC42 gene.- Function :...
, which are important for cell motility through modulation of the actin cytoskeleton. Bves also interacts with VAMP3
VAMP3
Vesicle-associated membrane protein 3 is a protein that in humans is encoded by the VAMP3 gene.-Interactions:VAMP3 has been shown to interact with* BCAP31,* BVES,* SNAP23,* STX4,* STX6.-Further reading:...
, a SNARE
Snare
Snare may refer to:* Snare trap, a kind of trap used for capturing animals* Snare drum* SNARE , a family of proteins involved in vesicle fusion* The Snares, a group of islands approximately 200 kilometres south of New Zealand...
protein important for vesicle fusion. Additionally, Bves has been shown to interact with the tight junction protein, ZO1
Tight junction protein 1
Tight junction protein ZO-1 is a protein that in humans is encoded by the TJP1 gene.-Interactions:Tight junction protein 1 has been shown to interact with F11 receptor, Gap junction protein, alpha 1, MLLT4, Occludin, TJP3, GJA3, KIRREL, Tight junction protein 2 and GJA8.-Further reading:...
, although this interaction is most likely via a protein complex, as a direct physical interaction has never been demonstrated.
Function
Disruption of Bves results in a wide range of cellular and developmental phenotypes. Grossly, cell motility and cell adhesion are impaired. Only recently have the molecular mechanisms underlying the function of Bves been uncovered.Bves modulates Rho GTPases through interaction with GEFT
Bves has been shown to interact and co-localize with GEFT, a modulator of Rho GTPaseRho family of GTPases
The Rho family of GTPases is a family of small signaling G protein , and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic organisms including yeasts and some plants...
signaling cascades. Disruption of Bves results in decreased cell speed and increased cell roundness, which are cell processes modulated by the Rho GTPases, Rac1 and Cdc42. Accordingly, Bves disruption results in decreased active Rac1 and Cdc42. Taken together, these data demonstrate that Bves modulates Rho GTPase signaling cascades through interaction with GEFT to affect cell movement and morphology.
Bves regulates vesicular transport via interaction with VAMP3
Bves has been shown to interact with VAMP3VAMP3
Vesicle-associated membrane protein 3 is a protein that in humans is encoded by the VAMP3 gene.-Interactions:VAMP3 has been shown to interact with* BCAP31,* BVES,* SNAP23,* STX4,* STX6.-Further reading:...
, a member of the SNARE
SNARE (protein)
SNARE proteins are a large protein superfamily consisting of more than 60 members in yeast and mammalian cells....
complex that facilitates vesicle fusion. VAMP3 is important for recycling of integrin
Integrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
s during cell migration and is also necessary for exocytosis of transferrin
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...
. Upon Bves disruption, cell rounding is increased, a phenotype indicative of decreased adhesion and disruption of integrin function. Accordingly, Bves disruption results in impaired integrin recycling, phenocopying the result seen with inhibition of VAMP3. Similarly, disruption of either Bves results in impaired transferrin recycling again, mimicking the result seen with disruption of VAMP3. Thus, Bves is important for VAMP3-mediated vesicular transport underlying cell migration and transferrin recycling.