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Gene Review

RASD2  -  RASD family, member 2

Homo sapiens

Synonyms: GTP-binding protein Rhes, MGC:4834, Ras homolog enriched in striatum, Rhes, TEM2, ...
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Disease relevance of RASD2


High impact information on RASD2

  • Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these beta-lactamases [6].
  • We show that in PC12 cells, Rhes is targeted to the plasma membrane by farnesylation [7].
  • However, Rhes is not transforming in murine fibroblasts [7].
  • The cyclic acyl phosph(on)ates, 1-hydroxy-5-phenyl-2,6-dioxaphosphorinone(3)-1-oxide, its 4-phenyl isomer, and the phosphonate (2-oxo) analogue of the latter inhibited typical class A (TEM-2) and class C (Enterobacter cloacae P99) beta-lactamases in a time-dependent fashion [8].
  • The amino acid sequence deduced from the corresponding bla gene showed two amino acid replacements with respect to the TEM-2 sequence: Glu-104 to Lys and His-153 to Arg [9].

Chemical compound and disease context of RASD2


Biological context of RASD2

  • The human homolog was found in a genomic sequence from human chromosome 22q13.1 and shares 95% identity with rat Rhes [12].
  • Recently, reports from several countries have pointed to the clinical relevance of 'extended-spectrum enzymes' derived by point mutation from the 'classical' TEM-1 or TEM-2 enzymes [13].
  • Resistance phenotypes were consistent with overproduction of TEM-1, TEM-2 or SHV-1 beta-lactamases in 56 strains, with AmpC cephalosporinase hyperproduction in 46 strains, and with production of inhibitor-resistant penicillinases in 49 strains [14].
  • The probe hybridized only with TEM-2 and OXA-2 class plasmids [15].
  • ME1228 was not hydrolyzed by TEM-1, TEM-2, SHV-1, and S. aureus plasmid beta-lactamases and was stable against hydrolysis by Richmond-Sykes type 1a, 1c, 1d, and IV chromosomal beta-lactamases [16].

Anatomical context of RASD2


Associations of RASD2 with chemical compounds

  • Rhes/RASD2 is a novel Ras homolog with almost restricted expression in the brain and highly enriched in the striatum, where it is controlled by thyroid hormone during the postnatal period [18].
  • Although Rhes was not induced by dexamethasone, its full expression is dependent upon thyroid hormone availability [12].
  • Rhes is shown to be expressed in beta-cells and its expression is regulated by efaroxan under conditions when a structurally related molecule, KU14R, is ineffective [17].
  • It was concluded that resistance to aztreonam and cefuroxime in these isolates was conferred by a beta-lactamase distinct from TEM-1, TEM-2 and SHV-1, but possibly derived from TEM-like enzymes [19].
  • All the enzymes were inhibited well by clavulanic acid, with I50 values ranging from 4.3 to 12 nM, compared to 130 nM for TEM-2 [20].

Regulatory relationships of RASD2

  • Little is known about its biochemical properties and cell signaling function, but the data available so far indicate that Rhes is constitutively bound to GTP and activates PI3K, and, on the other hand, interferes with cAMP/PKA pathway activation induced by G protein-coupled receptors [18].

Other interactions of RASD2

  • The expressions of TEM-2 and TEM-6 were found to be not significantly different between tumor tissues and normal tissues (P > 0.05) [21].
  • A TEM-2 derivative, TEM-201, with characteristics similar to those of TEM-7 was selected spontaneously in the presence of ceftazidime in vitro [22].
  • Cross-hybridization was observed between TEM-1 and TEM-2 or TLE-1, between SHV-1 and SHV-2, between OXA-1 and OXA-4, between OXA-2 and OXA-3 (weak), between PSE-2 and OXA-6 or OXA-5 (weak), and among PSE-1, PSE-4, and CARB-3 [23].


  1. Bacteriostatic and bactericidal activity of penicillins at constant and variable concentrations. Bauernfeind, A. Drugs (1985) [Pubmed]
  2. TEM-72, a new extended-spectrum beta-lactamase detected in Proteus mirabilis and Morganella morganii in Italy. Perilli, M., Segatore, B., de Massis, M.R., Riccio, M.L., Bianchi, C., Zollo, A., Rossolini, G.M., Amicosante, G. Antimicrob. Agents Chemother. (2000) [Pubmed]
  3. Stability in the presence of widespread beta-lactamases. A prerequisite for the antibacterial activity of beta-lactam drugs. Schito, G.C., Pesce, A., Debbia, E.A. Drugs (1994) [Pubmed]
  4. Antimicrobial activity and beta-lactamase stability of foramidocillin. Mandell, W., Neu, H.C. Antimicrob. Agents Chemother. (1986) [Pubmed]
  5. Comparative in vitro activity and beta-lactamase stability of FK482, a new oral cephalosporin. Neu, H.C., Saha, G., Chin, N.X. Antimicrob. Agents Chemother. (1989) [Pubmed]
  6. Extended-spectrum beta-lactamases: a clinical update. Paterson, D.L., Bonomo, R.A. Clin. Microbiol. Rev. (2005) [Pubmed]
  7. The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors. Vargiu, P., De Abajo, R., Garcia-Ranea, J.A., Valencia, A., Santisteban, P., Crespo, P., Bernal, J. Oncogene (2004) [Pubmed]
  8. Inhibition of beta-lactamases by monocyclic acyl phosph(on)ates. Kaur, K., Adediran, S.A., Lan, M.J., Pratt, R.F. Biochemistry (2003) [Pubmed]
  9. Characterization of TEM-56, a novel beta-lactamase produced by a Klebsiella pneumoniae clinical isolate. Neuwirth, C., Labia, R., Siebor, E., Pechinot, A., Madec, S., Chaibi, E.B., Kazmierczak, A. Antimicrob. Agents Chemother. (2000) [Pubmed]
  10. Correlation of the effect of beta-lactamase inhibitors on the beta-lactamase in growing cultures of gram-negative bacteria with their effect on the isolated beta-lactamase. Easton, C.J., Knowles, J.R. Antimicrob. Agents Chemother. (1984) [Pubmed]
  11. Val-237 for Ala substitution in the TEM-2 beta-lactamase dramatically alters the catalytic efficiencies towards carbenicillin and ticarcillin. Barthélémy, M., Péduzzi, J., Rowlands, D., Paul, G., Moreau, G., Labia, R. FEMS Microbiol. Lett. (1994) [Pubmed]
  12. Rhes: A striatal-specific Ras homolog related to Dexras1. Falk, J.D., Vargiu, P., Foye, P.E., Usui, H., Perez, J., Danielson, P.E., Lerner, D.L., Bernal, J., Sutcliffe, J.G. J. Neurosci. Res. (1999) [Pubmed]
  13. Importance of beta-lactamase stability in treating today's respiratory tract infections. Cullmann, W. Respiration; international review of thoracic diseases. (1993) [Pubmed]
  14. Mechanisms of reduced susceptibility to amoxycillin-clavulanic acid in Escherichia coli strains from the health region of Tortosa (Catalonia, Spain). Pérez-Moreno, M.O., Pérez-Moreno, M., Carulla, M., Rubio, C., Jardí, A.M., Zaragoza, J. Clin. Microbiol. Infect. (2004) [Pubmed]
  15. A gene probe for TEM type beta-lactamases. Cooksey, R.C., Clark, N.C., Thornsberry, C. Antimicrob. Agents Chemother. (1985) [Pubmed]
  16. In vitro activity of ME1228, a new parenteral cephalosporin. Neu, H.C., Saha, G., Chin, N.X. Antimicrob. Agents Chemother. (1989) [Pubmed]
  17. Identification of the monomeric G-protein, Rhes, as an efaroxan-regulated protein in the pancreatic beta-cell. Chan, S.L., Monks, L.K., Gao, H., Deaville, P., Morgan, N.G. Br. J. Pharmacol. (2002) [Pubmed]
  18. Analysis of rhes activation state and effector function. Bernal, J., Crespo, P. Meth. Enzymol. (2005) [Pubmed]
  19. Characterization of Klebsiella oxytoca septicaemia isolates resistant to aztreonam and cefuroxime. Wu, S.W., Dornbusch, K., Göransson, E., Ransjö, U., Kronvall, G. J. Antimicrob. Chemother. (1991) [Pubmed]
  20. Biochemical characteristics of extended broad spectrum beta-lactamases. Bush, K., Singer, S.B. Infection (1989) [Pubmed]
  21. Prognostic values of tumor endothelial markers in patients with colorectal cancer. Rmali, K.A., Puntis, M.C., Jiang, W.G. World J. Gastroenterol. (2005) [Pubmed]
  22. Plasmid-mediated beta-lactamase (TEM-7) involved in resistance to ceftazidime and aztreonam. Gutmann, L., Kitzis, M.D., Billot-Klein, D., Goldstein, F., Tran Van Nhieu, G., Lu, T., Carlet, J., Collatz, E., Williamson, R. Rev. Infect. Dis. (1988) [Pubmed]
  23. Detection of plasmid-mediated beta-lactamases with DNA probes. Huovinen, S., Huovinén, P., Jacoby, G.A. Antimicrob. Agents Chemother. (1988) [Pubmed]
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