Taxonomic distribution of proteins containing RAS domains

The RAS domain within your query sequence starts at position 1 and ends at position 166, and its E-value is 1.12e-122.

Ras signalling and apoptosis.

Downward J
Curr Opin Genet Dev. 1998; 8: 49-54

Activated Ras proteins have either positive or negative effects on the regulation of apoptosis depending on cell type and other factors. In part, this is due to the ability of Ras to control directly multiple effector pathways, including PI3-kinase, which provides a universal survival signal, and Raf, which can inhibit survival. The mechanisms remain partly unclear, however, especially with regard to Raf effects on apoptosis regulation. Recently Ras has been shown to be able to protect cells from apoptosis either through activation of PKB/Akt via PI3-kinase, or through activation of NF-kappa B.

Ras versus cyclin-dependent kinase inhibitors.

Lloyd AC
Curr Opin Genet Dev. 1998; 8: 43-8

In the past year, complex interactions between Ras and the cell cycle have been identified. In primary cells, activated Ras induces a cell-cycle arrest via the induction of cyclin-dependent kinase inhibitors (CDKIs). Oncogenic changes that cooperate with Ras act by neutralising CDKIs by various mechanisms. In the absence of a negative growth signal from Ras, such as in most immortalised cell lines, Ras acts positively on the cell cycle. Insights have been made into the mechanisms by which Ras abrogates remaining cell-cycle controls.

The structure of Ras protein: a model for a universal molecular switch.

Wittinghofer A, Pai EF
Trends Biochem Sci. 1991; 16: 382-7

X-ray crystallography has revealed the molecular architecture of the cellular and oncogenic forms of p21Ha-ras, the protein encoded by the human Ha-ras gene, in both its active (GTP-bound) and in its inactive (GDP-bound) forms. From comparison of these two structures, a mechanism is suggested for the GTPase hydrolysis reaction that triggers the conformational change necessary for signal transduction. The structures have also allowed identification of the structural consequences of point mutations and the way in which they interfere with the intrinsic GTPase activity of p21ras. The p21ras structure is similar to that of the G-domain of elongation factor Tu (EF-Tu) from Escherichia coli, suggesting that p21ras can serve as a good model for other guanine nucleotide binding proteins.

Time-resolved X-ray crystallographic study of the conformational change in Ha-Ras p21 protein on GTP hydrolysis.

Schlichting I, Almo SC, Rapp G, Wilson K, Petratos K, Lentfer A, Wittinghofer A, Kabsch W, Pai EF, Petsko GA, etal.
Nature. 1990; 345: 309-15

Crystals of Ha-Ras p21 with caged GTP at the active site have been used to investigate the conformational changes of p21 on GTP hydrolysis. The structure of the short-lived p21.GTP complex was determined by Laue diffraction methods. After GTP hydrolysis, substantial structural changes occur in the parts of the molecule implicated in the interaction with GTPase-activating protein. The trigger for this process seems to be a change in coordination of the active-site Mg2+ ion as a result of loss of the gamma-phosphate of GTP.

Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation.

Pai EF, Kabsch W, Krengel U, Holmes KC, John J, Wittinghofer A
Nature. 1989; 341: 209-14

The crystal structure of the guanine-nucleotide-binding domain of p21 (amino acids 1-166) complexed to the guanosine triphosphate analogue guanosine-5'-(beta, gamma-imido)triphosphate (GppNp) has been determined at a resolution of 2.6 A. The topological order of secondary structure elements is the same as that of the guanine-nucleotide-binding domain of bacterial elongation factor EF-Tu. Many interactions between nucleotide and protein have been identified. The effects of point mutations and the conservation of amino-acid sequence in the guanine-nucleotide-binding proteins are discussed.

Guanine nucleotide-binding and autophosphorylating activities associated with the p21src protein of Harvey murine sarcoma virus.

Shih TY, Papageorge AG, Stokes PE, Weeks MO, Scolnick EM
Nature. 1980; 287: 686-91

The purified p21src protein of Harvey sarcoma virus shows a guanine nucleotide-binding activity and, in addition, at elevated temperature an autophosphorylating activity at a threonine residue using as phosphoryl donor GTP or dGTP but not ATP or dATP. These biochemical activities are unique among those associated with transforming proteins of RNA-containing or DNA-containing tumour viruses.