The reference OMIM entry for this protein is 602049

Ras-related c3 botulinum toxin substrate 2; rac2
Rho family, small gtp-binding protein rac2

CLONING

Members of the RAS superfamily of small GTP-binding proteins (see 190020) appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Didsbury et al. (1989) identified 2 human cDNAs, called RAC1 (602048) and RAC2 by them, that are 92% identical and share 58% and 26 to 30% amino acid identity with human RHOS and RAS, respectively. The 2 genes encode the C-terminal consensus sequence (CXXX-COOH), which localizes RAS to the inner plasma membrane, and the residues gly12 and ala59, at which sites mutations elicit transforming potential to RAS. RAC2 mRNA displayed relative myeloid tissue selectivity and showed an increase upon differentiation of HL-60 and U937 cells to neutrophil-like and monocyte-like morphology, respectively. Using transfection experiments, Didsbury et al. (1989) showed that RAC1 and RAC2 are substrates for ADP-ribosylation by the C3 component of botulinum toxin. See also RAC3 (602050).

GENE FUNCTION

Using a cDNA subtraction method, representational display analysis, Li et al. (2000) showed that Rac2 is selectively expressed in mouse type 1 helper T lymphocytes (Th1). Rac2 induces the interferon-gamma (147570) promoter through cooperative interaction of the NF-kappa-B (164011) and p38 MAP kinase (600289) pathways. Diebold and Bokoch (2001) showed that RAC2 is required for the transfer of electrons from NADPH to cytochrome b-associated FAD, then to cytochrome b heme, and finally to oxygen. Using site-specific mutants, they showed that RAC2 acts independently of p67-phox (233710) to regulate the initial transfer of electrons from NADPH to FAD and that RAC2 binding to p67-phox is necessary to complete electron transfer to molecular oxygen to form superoxide anion. Gu et al. (2002) found that the expression of 38 known genes was significantly altered in Rac2 -/- mouse mast cells after cytokine stimulation compared with those of wildtype cells. Of these, Mcp7 (TPSAB1; 191080) transcription in wildtype cells was increased 4-fold after stimulation with stem cell factor (SCF) (KITLG; 184745); however, in spite of a compensatory Rac1 increase in Rac2-deficient cells, SCF-induced Mcp7 transcription did not occur in these cells. Gu et al. (2002) concluded that in Rac2 -/- mast cells loss of Mcp7 induction was due to reduced Jnk (see MAPK8; 601158) activity but not due to reduced NFKB (see 164011) activity. By studying host responses to E. coli cytotoxic necrotizing factor-1 (CNF1) in Drosophila and human cells, Boyer et al. (2011) showed that the host indirectly sensed the pathogen via its modification and activation of RAC2. After CNF1 modified RAC2, RAC2 interacted with the innate immune adaptors Imd and RIPK1 (603453)-RIPK2 (603455) in flies and human cells, respectively. Induction of the immune response in flies required CNF1 enzymatic activity, which, in mammals, catalyzes deamidation of a glutamine to glutamic acid in RAC2, abolishing GTPase activity and locking the enzyme into an active form. Modified RAC2 interacted with RIPK1 and RIPK2 to induce immune activation via NFKB and IL8 (146930) expression in human cells. Boyer et al. (2011) concluded that virulence factors such as CNF1 induce an immune response through this mechanism, whereas avirulent microbes fail to provoke host responses.

GENE STRUCTURE

Courjal et al. (1997) determined that RAC2 is made up of at least 7 exons, spanning ov ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 602049 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).