GAPs galore! A survey of putative Ras superfamily GTPase activating proteins in man and Drosophila.
Typical members of the Ras superfamily of small monomeric GTP-binding proteins function as regulators of diverse processes by cycling between biologically active GTP- and inactive GDP-bound conformations. Proteins that control this cycling include guanine nucleotide exchange factors or GEFs, which activate Ras superfamily members by catalyzing GTP for GDP exchange, and GTPase activating proteins or GAPs, which accelerate the low intrinsic GTP hydrolysis rate of typical Ras superfamily members, thus causing their inactivation. Two among the latter class of proteins have been implicated in common genetic disorders associated with an increased cancer risk, neurofibromatosis-1, and tuberous sclerosis. To facilitate genetic analysis, I surveyed Drosophila and human sequence databases for genes predicting proteins related to GAPs for Ras superfamily members. Remarkably, close to 0.5% of genes in both species (173 human and 64 Drosophila genes) predict proteins related to GAPs for Arf, Rab, Ran, Rap, Ras, Rho, and Sar family GTPases. Information on these genes has been entered into a pair of relational databases, which can be used to identify evolutionary conserved proteins that are likely to serve basic biological functions, and which can be updated when definitive information on the coding potential of both genomes becomes available.
Bernards
André
A
Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, MA 02129-2000, USA. abernard@helix.mgh.harvard.edu
D020727:ADP-Ribosylation Factors / Q000235:genetics; D000818:Animals; D030541:Databases, Genetic; D004330:Drosophila; D020690:GTPase-Activating Proteins / Q000235:genetics; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D013379:Substrate Specificity; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins / Q000235:genetics; D020931:ran GTP-Binding Protein / Q000235:genetics; D020668:rap GTP-Binding Proteins / Q000235:genetics; D020703:ras GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics*; D020741:rho GTP-Binding Proteins / Q000235:genetics
C503237:ARFGAP1 protein, human; C503240:ARFGAP3 protein, human; D020690:GTPase-Activating Proteins; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D020703:ras GTPase-Activating Proteins; C085379:rho GTPase-activating protein; D020727:ADP-Ribosylation Factors; D020559:Monomeric GTP-Binding Proteins; C077395:SAR1 protein, S cerevisiae; D020691:rab GTP-Binding Proteins; D020931:ran GTP-Binding Protein; D020668:rap GTP-Binding Proteins; D020741:rho GTP-Binding Proteins