Small GTPase Superfamily
Small GTPase SuperfamilyThe small GTPase superfamily comprises monomeric GTP-binding proteins with molecular masses usually in the range of 20-25 kDa. The small GTPase superfamily has been found in all eukaryotic organisms, ranging from Giardia to human (See Weeks et al. in Dictyostelium Genomics). Members of the superfamily share approx 30% amino acid sequence identity, with the bulk of this identity derived from four highly conserved domains required for the recognition of GDP, GTP and for GTPase activity. The small GTPase superfamily is synonymous with the Ras superfamily, this latter name derived from the Ras protein, the first member of the superfamily to be described.
Small GTPases exist as monomers which function as molecular switches in intracellular signaling to control a wide variety of cellular functions. In general the GDP-bound form is the inactive configuration of the molecular switch, while the GTP-bound form is active. The switch is activated by the exchange of GDP for GTP, catalyzed by guanine nucleotide exchange factors (GEFs), in response to a variety of upstream signal signals. Activated GTPases then interact with one or more effector proteins, leading to activation of downstream signaling pathways. GTPase activating proteins (GAPs) stimulate an otherwise low intrinsic GTPase activity, reverting the conformation back to the inactive GDP-bound form. The process of activation and inactivation is repeated as long as the upstream stimulatory signal is present.
Most of the small GTPase superfamily members can be classified into 5 distinct subfamilies: Ras, Rho/Rac, Rab, Arf/Sar1 and Ran. Members within each subfamily share of the order of 40% or more amino acid sequence identity and exhibit conserved motifs required for interaction with specific classes of downstream effectors. For full details of the small GTPase superfamily in the Dictyostelium genome see Weeks et al. in Dictyostelium Genomics
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