RAC3 (ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3))

Note	The Rac3 gene encodes a single protein of 192 amino acid residues.
	Schematic representation of the Rac3 protein (not to scale). Mutations that generate mutants that are locked in a certain conformation - constitutively active or dominant negative - are shown. The C-terminal end contains the CTVM motif that is post-translationally modified the three last amino acid residues are removed and the C residue is geranyl-geranylated.
Description	Rac3 is a small 21 kDa GTPase that acts as a molecular switch. In its active form, it is bound to GTP, whereas it is inactive in its GDP-bound form. Racs are controlled by guanidine activating proteins (GEFs) that exchange bound GDP for GTP and by GTPase activating proteins (GAPs) that promote GTP hydrolysis. Because of the hydrophobic isoprenyl moiety at the C-terminal end, it is associated with membranes. In the cytoplasm it associates with the chaperone RhoGDI.
Expression	Rac3 mRNA was reported in human cell lines including GM04155 (lymphoblastic leukemia), K562 (CML), 5838 (Ewing sarcoma), HL60 (promyelocytic leukemia) and DU4475 (breast cancer). Rac3 expression was reported using semi-quantitative RT/PCR in gastric tumor and adjacent normal tissue as well as gastric cancer cell lines. Expression of Rac3 using RT/PCR (38 cycles) was reported in human brain, liver, kidney and pancreas poly A RNA and also 19% of brain tumors expressed Rac3 mRNA. Rac3-specific polyclonal antibodies were used to show Rac3 protein in the brain (deep cerebellar nuclei and the pons) in 7 day old mice. Low level expression of mouse rac3 has been reported in bone-marrow-derived monocytes and in B-lineage lymphoblasts using standard and RealTime RT/PCR.
Localisation	The Rac3 protein is located on endomembranes and cell membranes.
Function	Rac proteins regulate a variety of functions including cytoskeletal organization, cell cycle, reactive oxygen species production, and vesicle trafficking. In cultured cells they also are involved in cellular transformation. Studies of null mutant Rac3 mice showed that Rac3 regulates cerebellar functions and in a mouse model plays a role in leukemia development caused by the Bcr/Abl oncogene. Point mutations (N26D, F37L, Y40C, N43D) were introduced into different critical residues of the effector domain of Rac3 and the effects of these were investigated on the ability of Rac3 to regulate membrane ruffles, c-jun activation and transformation. Transformation was assayed as the ability to cooperate with activated Raf in focus formation of NIH3T3 cells and the ability to promote growth of these cells in soft agar.
Homology	Rac3 is most closely related to Rac1 and Rac2. On a nucleotide level human Rac3 has 77% identity with Rac1, 83% identity with Rac2 and 69% identity with RhoG. On an amino acid level, Rac3 and Rac1 differ in 14/192 residues (92% identical), whereas Rac3 and Rac2 differ in 22/192 residues (89% identical). Rac belongs to the extended Rho family of small G-proteins. Biochemically, Rac1 and Rac3 are closely related.

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