Alternative titles; symbols
HGNC Approved Gene Symbol: RRAS
Cytogenetic location: 19q13.33 Genomic coordinates (GRCh38): 19:49,635,292-49,640,143 (from NCBI)
Lowe et al. (1987) isolated the human RRAS gene by low-stringency hybridization with a Harvey-ras probe. They found that the predicted 218-amino acid RRAS protein has an amino-terminal extension of 26 residues compared with HRAS p21 (190020) and shares 55% sequence identity with it. The cloned mouse Rras cDNA encodes a predicted protein sharing 94.5% sequence identity with the human protein.
By immunostaining several mouse tissues, Komatsu and Ruoslahti (2005) found that Rras was primarily expressed in vascular smooth muscle cells in small arterioles and major arteries and in endothelial cells of lung capillaries. Lower Rras levels were found in smooth muscle cells of veins, renal glomeruli, and venous endothelium of spleen. In smooth muscle cells, Rras was distributed along the plasma membrane.
Oinuma et al. (2004) reported that the semaphorin-4D (SEMA4D; 601866) receptor plexin B1 (601053) directly stimulates the intrinsic GTPase activity of RRAS, a member of the Ras superfamily of small GTP-binding proteins that has been implicated in promoting cell adhesion and neurite outgrowth. This activity required the interaction of plexin B1 with RND1 (609038), a small GTP-binding protein of the Rho family. Downregulation of RRAS activity by the plexin B1/RND1 complex was essential for the SEMA4D-induced growth cone collapse in hippocampal neurons. Oinuma et al. (2004) concluded that plexin B1 mediates SEMA4D-induced repulsive axon guidance signaling by acting as a GTPase-activating protein for RRAS.
Lowe et al. (1987) determined that the RRAS gene has at least 6 exons.
Komatsu and Ruoslahti (2005) found that Rras-null mice were viable and fertile with no obvious abnormalities and normal tissues upon histologic examination. However, Rras-null mice showed exaggerated neointimal thickening in response to arterial injury and increased angiogenesis in implanted tumors. In wildtype mice, Rras expression was greatly reduced in hyperplastic neointimal smooth muscle cells and in angiogenic endothelial cells. Overexpression of activated Rras suppressed mitogenic and invasive activities of growth factor-stimulated vascular cells.
By means of a panel of mouse-human somatic cell hybrids, Lowe et al. (1987) mapped the human RRAS gene to chromosome 19. By means of a panel of mouse-hamster somatic cell hybrids, they mapped the mouse homolog to chromosome 7.
Komatsu, M., Ruoslahti, E. R-Ras is a global regulator of vascular regeneration that suppresses intimal hyperplasia and tumor angiogenesis. Nature Med. 11: 1346-1350, 2005. [PubMed: 16286923] [Full Text: https://doi.org/10.1038/nm1324]
Lowe, D. G., Capon, D. J., Delwart, E., Sakaguchi, A. Y., Naylor, S. L., Goeddel, D. V. Structure of the human and murine R-ras genes, novel genes closely related to ras proto-oncogenes. Cell 48: 137-146, 1987. [PubMed: 3098437] [Full Text: https://doi.org/10.1016/0092-8674(87)90364-3]
Oinuma, I., Ishikawa, Y., Katoh, H., Negishi, M. The semaphorin 4D receptor plexin-B1 is a GTPase activating protein for R-Ras. Science 305: 862-865, 2004. [PubMed: 15297673] [Full Text: https://doi.org/10.1126/science.1097545]