Blood vessel epicardial substance

Last updated
BVES
Identifiers
Aliases BVES , HPOP1, POPDC1, LGMD2X, blood vessel epicardial substance, CARICK, LGMDR25
External IDs OMIM: 604577 MGI: 1346013 HomoloGene: 48497 GeneCards: BVES
Orthologs
SpeciesHumanMouse
Entrez

11149

23828

Ensembl

ENSG00000112276

ENSMUSG00000071317

UniProt

Q8NE79

Q9ES83

RefSeq (mRNA)

NM_001199563
NM_007073
NM_147147

NM_024285

RefSeq (protein)

NP_001186492
NP_009004
NP_671488

NP_077247

Location (UCSC) Chr 6: 105.1 – 105.14 Mb Chr 10: 45.21 – 45.25 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Blood vessel epicardial substance (BVES) also known as popeye domain-containing protein 1 (POPDC1) is a protein that is encoded by the BVES gene in humans. [5] [6]

Contents

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. [7] [8] [9] [10] 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. [11] [12] [13]

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). [6] [14] Although initially isolated from cardiac tissue, it was later revealed that Bves is highly expressed in muscle, epithelial and brain tissue. [8] 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. [7] [8] [9]

Structure

Bves is a three-pass transmembrane protein with a short extracellular N-terminus (~40aa) and a larger intracellular C-terminus (~250aa). [15] 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. [16]

Localization/expression

Bves is expressed in muscle, epithelial and brain tissue, and is thus found in many adult organs. [9] During development, Bves is detected in all three germ layers and later localizes to the aforementioned tissues. [17] 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. [11]

Interacting proteins

Bves interacts with GEFT, a protein that modulates Rho GTPases, Rac1 and Cdc42, which are important for cell motility through modulation of the actin cytoskeleton. [13] Bves also interacts with VAMP3, a SNARE protein important for vesicle fusion. [10] 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. [11]

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.

Modulation of Rho GTPases

Bves has been shown to interact and co-localize with GEFT, a modulator of Rho GTPase 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. [13]

Regulation of vesicular transport

Bves has been shown to interact with VAMP3, a member of the SNARE complex that facilitates vesicle fusion. VAMP3 is important for recycling of integrins during cell migration and is also necessary for exocytosis of transferrin. [18] [19] [20] [21] [22] 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. [10]

Silencing in malignancy

Bves is silenced by promoter hypermethylation in malignancy. Bves is underexpressed in colon, lung, and breast cancer. In colon cancer this occurs very early during tumorigenesis, with Bves underexpression first noted in premalignant adenomas.

Related Research Articles

<span class="mw-page-title-main">Guanine nucleotide exchange factor</span> Proteins which remove GDP from GTPases

Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity. Some GEFs can activate multiple GTPases while others are specific to a single GTPase.

The Rho family of GTPases is a family of small signaling G proteins, 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 kingdoms, including yeasts and some plants. Three members of the family have been studied in detail: Cdc42, Rac1, and RhoA. All G proteins are "molecular switches", and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions.

<span class="mw-page-title-main">CDC42</span> Protein-coding gene in the species Homo sapiens

Cell division control protein 42 homolog is a protein that in humans is encoded by the CDC42 gene. Cdc42 is involved in regulation of the cell cycle. It was originally identified in S. cerevisiae (yeast) as a mediator of cell division, and is now known to influence a variety of signaling events and cellular processes in a variety of organisms from yeast to mammals.

<span class="mw-page-title-main">RAC1</span> Protein-coding gene in the species Homo sapiens

Rac1, also known as Ras-related C3 botulinum toxin substrate 1, is a protein found in human cells. It is encoded by the RAC1 gene. This gene can produce a variety of alternatively spliced versions of the Rac1 protein, which appear to carry out different functions.

<span class="mw-page-title-main">Transforming protein RhoA</span> Protein and coding gene in humans

Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. It acts upon several effectors. Among them, ROCK1 and DIAPH1 are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.

<span class="mw-page-title-main">RAC3</span> Mammalian protein found in Homo sapiens

Ras-related C3 botulinum toxin substrate 3 (Rac3) is a G protein that in humans is encoded by the RAC3 gene. It is an important component of intracellular signalling pathways. Rac3 is a member of the Rac subfamily of the Rho family of small G proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.

<span class="mw-page-title-main">GPR97</span> Protein-coding gene in the species Homo sapiens

G-protein coupled receptor 97 also known as adhesion G protein-coupled receptor G3 (ADGRG3) is a protein that in humans is encoded by the ADGRG3 gene. GPR97 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

<span class="mw-page-title-main">IQGAP1</span>

Ras GTPase-activating-like protein IQGAP1 (IQGAP1) also known as p195 is a ubiquitously expressed protein that in humans is encoded by the IQGAP1 gene. IQGAP1 is a scaffold protein involved in regulating various cellular processes ranging from organization of the actin cytoskeleton, transcription, and cellular adhesion to regulating the cell cycle.

<span class="mw-page-title-main">ARHGEF7</span> Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor 7 is a protein that in humans is encoded by the ARHGEF7 gene.

<span class="mw-page-title-main">DLC1</span> Protein-coding gene in the species Homo sapiens

Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans is encoded by the DLC1 gene.

<span class="mw-page-title-main">VAMP3</span> Protein-coding gene in the species Homo sapiens

Vesicle-associated membrane protein 3 is a protein that in humans is encoded by the VAMP3 gene.

<span class="mw-page-title-main">Integrin beta 8</span> Protein-coding gene in the species Homo sapiens

Integrin beta-8 is a protein that in humans is encoded by the ITGB8 gene.

<span class="mw-page-title-main">IQGAP2</span> Protein-coding gene in the species Homo sapiens

Ras GTPase-activating-like protein IQGAP2 is an enzyme that in humans is encoded by the IQGAP2 gene.

Rac is a subfamily of the Rho family of GTPases, small signaling G proteins. Just as other G proteins, Rac acts as a molecular switch, remaining inactive while bound to GDP and activated once GEFs remove GDP, permitting GTP to bind. When bound to GTP, Rac is activated. In its activated state, Rac participates in the regulation of cell movement, through its involvement in structural changes to the actin Cytoskeleton. By changing the cytoskeletal dynamics within the cell, Rac-GTPases are able to facilitate the recruitment of neutrophils to the infected tissues, and to regulate degranulation of azurophil and integrin-dependent phagocytosis.

<span class="mw-page-title-main">CDC42EP2</span> Protein-coding gene in the species Homo sapiens

Cdc42 effector protein 2 is a protein that in humans is encoded by the CDC42EP2 gene.

<span class="mw-page-title-main">Cingulin-like protein 1</span> Protein found in humans

Cingulin-like protein 1, also known as paracingulin or junction-associated-coiled-coil protein (JACOP), is a protein which is encoded by the CGNL1 gene.

<span class="mw-page-title-main">Clostridium difficile toxin A</span>

Clostridium difficile toxin A (TcdA) is a toxin generated by Clostridioides difficile, formerly known as Clostridium difficile. It is similar to Clostridium difficile Toxin B. The toxins are the main virulence factors produced by the gram positive, anaerobic, Clostridioides difficile bacteria. The toxins function by damaging the intestinal mucosa and cause the symptoms of C. difficile infection, including pseudomembranous colitis.

<span class="mw-page-title-main">ARHGAP31</span> Protein-coding gene in the species Homo sapiens

The Rho GTPase activating protein 31 is encoded in humans by the ARHGAP31 gene. It is a Cdc42/Rac1 GTPase regulator.

<span class="mw-page-title-main">Rho gtpase activating protein 21</span> Protein-coding gene in the species Homo sapiens

Rho GTPase activating protein 21 is a protein that in humans is encoded by the ARHGAP21 gene.

<span class="mw-page-title-main">Abr, rhogef and gtpase activating protein</span> Protein-coding gene in the species Homo sapiens

ABR, RhoGEF and GTPase activating protein is a protein that in humans is encoded by the ABR gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000112276 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000071317 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Reese DE, Bader DM (Sep 1999). "Cloning and expression of hbves, a novel and highly conserved mRNA expressed in the developing and adult heart and skeletal muscle in the human". Mammalian Genome. 10 (9): 913–5. doi:10.1007/s003359901113. PMID   10441744. S2CID   35384190.
  6. 1 2 Andrée B, Hillemann T, Kessler-Icekson G, Schmitt-John T, Jockusch H, Arnold HH, Brand T (Jul 2000). "Isolation and characterization of the novel popeye gene family expressed in skeletal muscle and heart". Developmental Biology. 223 (2): 371–82. doi: 10.1006/dbio.2000.9751 . PMID   10882522.
  7. 1 2 Brand T (2005). "The Popeye domain-containing gene family". Cell Biochemistry and Biophysics . 43 (1): 95–103. doi:10.1385/CBB:43:1:095. PMID   16043887. S2CID   13142874.
  8. 1 2 3 Osler ME, Smith TK, Bader DM (Mar 2006). "Bves, a member of the Popeye domain-containing gene family". Developmental Dynamics. 235 (3): 586–93. doi:10.1002/dvdy.20688. PMC   2849751 . PMID   16444674.
  9. 1 2 3 Hager HA, Bader DM (Jun 2009). "Bves: ten years after". Histology and Histopathology. 24 (6): 777–87. PMC   2853719 . PMID   19337975.
  10. 1 2 3 Hager HA, Roberts RJ, Cross EE, Proux-Gillardeaux V, Bader DM (Feb 2010). "Identification of a novel Bves function: regulation of vesicular transport". The EMBO Journal. 29 (3): 532–45. doi:10.1038/emboj.2009.379. PMC   2830705 . PMID   20057356.
  11. 1 2 3 Osler ME, Chang MS, Bader DM (Oct 2005). "Bves modulates epithelial integrity through an interaction at the tight junction". Journal of Cell Science. 118 (Pt 20): 4667–78. doi: 10.1242/jcs.02588 . PMID   16188940.
  12. ↑ Ripley AN, Osler ME, Wright CV, Bader D (Jan 2006). "Xbves is a regulator of epithelial movement during early Xenopus laevis development". Proceedings of the National Academy of Sciences of the United States of America. 103 (3): 614–9. Bibcode:2006PNAS..103..614R. doi: 10.1073/pnas.0506095103 . PMC   1334639 . PMID   16407138.
  13. 1 2 3 Smith TK, Hager HA, Francis R, Kilkenny DM, Lo CW, Bader DM (Jun 2008). "Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity". Proceedings of the National Academy of Sciences of the United States of America. 105 (24): 8298–303. Bibcode:2008PNAS..105.8298S. doi: 10.1073/pnas.0802345105 . PMC   2423412 . PMID   18541910.
  14. ↑ Reese DE, Zavaljevski M, Streiff NL, Bader D (May 1999). "bves: A novel gene expressed during coronary blood vessel development". Developmental Biology. 209 (1): 159–71. doi: 10.1006/dbio.1999.9246 . PMID   10208750.
  15. ↑ Knight RF, Bader DM, Backstrom JR (Aug 2003). "Membrane topology of Bves/Pop1A, a cell adhesion molecule that displays dynamic changes in cellular distribution during development". The Journal of Biological Chemistry. 278 (35): 32872–9. doi: 10.1074/jbc.M301961200 . PMID   12815060.
  16. ↑ Kawaguchi M, Hager HA, Wada A, Koyama T, Chang MS, Bader DM (2008). "Identification of a novel intracellular interaction domain essential for Bves function". PLOS ONE. 3 (5): e2261. Bibcode:2008PLoSO...3.2261K. doi: 10.1371/journal.pone.0002261 . PMC   2373926 . PMID   18493308. Open Access logo PLoS transparent.svg
  17. ↑ Osler ME, Bader DM (Mar 2004). "Bves expression during avian embryogenesis". Developmental Dynamics. 229 (3): 658–67. doi: 10.1002/dvdy.10490 . PMID   14991721. S2CID   12458928.
  18. ↑ McMahon HT, Ushkaryov YA, Edelmann L, Link E, Binz T, Niemann H, Jahn R, Südhof TC (Jul 1993). "Cellubrevin is a ubiquitous tetanus-toxin substrate homologous to a putative synaptic vesicle fusion protein". Nature. 364 (6435): 346–9. Bibcode:1993Natur.364..346M. doi:10.1038/364346a0. PMID   8332193. S2CID   4324845.
  19. ↑ Proux-Gillardeaux V, Gavard J, Irinopoulou T, Mège RM, Galli T (May 2005). "Tetanus neurotoxin-mediated cleavage of cellubrevin impairs epithelial cell migration and integrin-dependent cell adhesion". Proceedings of the National Academy of Sciences of the United States of America. 102 (18): 6362–7. Bibcode:2005PNAS..102.6362P. doi: 10.1073/pnas.0409613102 . PMC   1088364 . PMID   15851685.
  20. ↑ Skalski M, Coppolino MG (Oct 2005). "SNARE-mediated trafficking of alpha5beta1 integrin is required for spreading in CHO cells". Biochemical and Biophysical Research Communications. 335 (4): 1199–210. doi:10.1016/j.bbrc.2005.07.195. PMID   16112083.
  21. ↑ Tayeb MA, Skalski M, Cha MC, Kean MJ, Scaife M, Coppolino MG (Apr 2005). "Inhibition of SNARE-mediated membrane traffic impairs cell migration". Experimental Cell Research. 305 (1): 63–73. doi:10.1016/j.yexcr.2004.12.004. PMID   15777788.
  22. ↑ Luftman K, Hasan N, Day P, Hardee D, Hu C (Feb 2009). "Silencing of VAMP3 inhibits cell migration and integrin-mediated adhesion". Biochemical and Biophysical Research Communications. 380 (1): 65–70. doi:10.1016/j.bbrc.2009.01.036. PMC   2716655 . PMID   19159614.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.