Alternative titles; symbols
HGNC Approved Gene Symbol: RASD2
Cytogenetic location: 22q12.3 Genomic coordinates (GRCh38) : 22:35,532,806-35,553,999 (from NCBI)
Using serial analysis of gene expression (SAGE), St. Croix et al. (2000) identified partial cDNAs corresponding to several tumor endothelial markers (TEMs) that displayed elevated expression during tumor angiogenesis. Among the genes they identified was TEM2.
Vargiu et al. (2004) determined that RHES, which contains 266 amino acids in rat and human, is a putative Ras (HRAS; 190020)-like monomeric G protein with an extended C-terminal domain compared with other Ras family proteins. It terminates in a conserved CAAX box (CTIQ in human) for targeting to the plasma membrane. RHES shares highest similarity with DEXRAS (RASD1; 605550). Northern blot analysis of several rat tissues detected high Rhes expression in brain, much lower expression in thyroid gland, and little to no expression in other tissues. In situ hybridization revealed prominent expression in striatum, in specific regions of the cortex, hippocampus, cerebellum, and thalamus, and in several brain nuclei. Fluorescence-tagged rat Rhes localized to the plasma membrane, which required farnesylation of the C-terminal CAAX box.
Using Northern blot analysis, Spano et al. (2004) found that expression of mouse Rhes was high in brain, low in kidney, thyroid, lung, heart, and testis, and absent in liver. RT-PCR detected Rhes expression beginning at mouse embryonic day 13.5.
The imidazoline compound efaroxan potentiates nutrient-induced insulin secretion from pancreatic beta cells. Chan et al. (2002) showed that efaroxan upregulated RHES expression in rat and human pancreatic beta cells.
Vargiu et al. (2004) found that about 30% of endogenous Rhes was bound to GTP in rat PC12 cells, and that the proportion bound to GTP was not affected by typical Ras family nucleotide exchange factors (e.g., SOS1; 182530). Rhes activated PI3 kinase (see 601232). In contrast, Rhes impaired activation of the cAMP/protein kinase A (see 601639) pathway by TSH (see TSHB; 188540) and by a constitutively active beta-2 adrenergic receptor (ADRB2; 109690) mutant by a mechanism that suggested uncoupling of the receptor to its cognate heterotrimeric G protein (see GNAS; 139320).
Agretti et al. (2007) showed that RHES inhibited basal and bovine TSH-stimulated cAMP production in COS-7 cells coexpressing RHES with TSH receptor (TSHR; 603372). This inhibition was due to reduced expression of TSHR at the cell surface. RHES also attenuated cAMP accumulation via ligand-induced activation of coexpressed FSH receptor (FSHR; 136435) and LH receptor (LHCGR; 152790).
Hartz (2009) mapped the RASD2 gene to chromosome 22q12.3 based on an alignment of the RASD2 sequence (GenBank AF279143) with the genomic sequence (build 36.1).
Spano et al. (2004) found that Rhes -/- mice were viable and appeared to develop normally, but they weighed less than wildtype mice and displayed minor behavioral abnormalities. Rhes -/- mice showed altered locomotor activity in an open-field test and performed worse than wildtype mice in the rota-rod test. Female Rhes -/- mice appeared more anxious than wildtype females.
Agretti, P., De Marco, G., Pinchera, A., Vitti, P., Bernal, J., Tonacchera, M. Ras homolog enriched in striatum inhibits the functional activity of wildtype thyrotropin, follicle-stimulating hormone, luteinizing hormone receptors and activating thyrotropin receptor mutations by altering their expression in COS-7 cells. J. Endocr. Invest. 30: 279-284, 2007. [PubMed: 17556863] [Full Text: https://doi.org/10.1007/BF03346294]
Chan, S. L. F., Monks, L. K., Gao, H., Deaville, P., Morgan, N. G. Identification of the monomeric G-protein, Rhes, as an efaroxan-regulated protein in the pancreatic beta-cell. Brit. J. Pharm. 136: 31-36, 2002. [PubMed: 11976265] [Full Text: https://doi.org/10.1038/sj.bjp.0704680]
Hartz, P. A. Personal Communication. Baltimore, Md. 6/9/2009.
Spano, D., Branchi, I., Rosica, A., Pirro, M. T., Riccio, A., Mithbaokar, P., Affuso, A., Arra, C., Campolongo, P., Terracciano, D., Macchia, V., Bernal, J., Alleva, E., Di Lauro, R. Rhes is involved in striatal function. Molec. Cell. Biol. 24: 5788-5796, 2004. [PubMed: 15199135] [Full Text: https://doi.org/10.1128/MCB.24.13.5788-5796.2004]
St. Croix, B., Rago, C., Velculescu, V., Traverso, G., Romans, K. E., Montgomery, E., Lal, A., Riggins, G. J., Lengauer, C., Vogelstein, B., Kinzler, K. W. Genes expressed in human tumor endothelium. Science 289: 1197-1202, 2000. [PubMed: 10947988] [Full Text: https://doi.org/10.1126/science.289.5482.1197]
Vargiu, P., De Abajo, R., Garcia-Ranea, J. A., Valencia, A., Santisteban, P., Crespo, P., Bernal, J. The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors. Oncogene 23: 559-568, 2004. [PubMed: 14724584] [Full Text: https://doi.org/10.1038/sj.onc.1207161]