The Rac2 gene sequence contains 7 exons (Courjal et al., 1997) and is expressed specifically in hematopoietic cells. Human Rac2 gene locus is silenced in non-hematopoietic cells by a mechanism that involves DNA methylation (Ladd et al., 2004). Cells that lack Rac2 expression exhibit increased cytosine methylation in the sequences flanking the gene, whereas cells that express Rac2 exhibit increased cytosine methylation within the body of the Rac2 gene.

The human Rac2 gene promoter lacks TATA and CCAAT boxes, utilizes multiple transcription initiation sites, and contains several putative Sp1 binding sites, which is common in promoters that lack TATA boxes (Ladd et al., 2004).
The transcript length is of 1471 nt translated to a 192 residues protein.

Rac2 protein belongs to the GTP-binding proteins of the Rho family and cycles between an active GTP-bound form and an inactive GDP-bound form. This regulatory cycle is exerted by three distinct families of proteins: guanine exchange factors (GEFs), GTPase-activating proteins (GAPs), and guanine nucleotide dissociation inhibitors (GDIs). Several GEFs have been shown to activate Rac2 selectively, Vav1 (Ming et al., 2007), Tiam1 (Haeusler et al., 2003), P-Rex1 (Welch et al., 2002), Swap70 (Sivalenka and Jessberger, 2004) and Dock2 (Nishihara et al., 2002). Two GAPs that act on Rac2 are Abr and Bcr (Chuang et al., 1995), as well as others found in leukocytes.
Rac2 function depends on association of the GTPase with membranes and subcellular localization, properties influenced by C-terminal lipid modifications, specifically is modified by the C20 GG isoprenoid.
Upon GTP loading, a conformational change takes place that allows Rac2 protein to interact with several downstream effectors that ultimately process the information and propagate the signal within the cell, causing changes in the actin cytoskeleton, release of inflammatory modulators and innate immunity. The signaling of active Rac2 is mediated by its interaction with effector proteins such as p67phox and cytochrome b-558 (Diebold and Bokoch, 2001), PLCbeta2 (Piechulek et al., 2005), nitric oxide synthase 2 (NOS2) (Kuncewicz et al., 2001) and Pak1 (Carstanjen et al., 2005).

Expression is restricted to hematopoietic cells and exhibits the highest expression in myeloid cells. Rac2 expression is regulated during the differentiation of hematopoietic and myeloid cells. There is some data suggesting that Rac2 might be expressed in tumors.

Once activated Rac2 is mainly localized in endomembranes.

As suggested by its restricted expression, Rac2 has a specialized role in many hematopoietic and immunological processes. Rac2 deficient mice show defects in stem cells, mast cells as well as B and T cells.
Role in hematopoietic stem-cell progenitor engraftment
The contribution of the GTPase Rac2 to the normal functioning of hematopoietic stem-cell progenitors (HSC/Ps) was addressed based on the phenotype of Rac2-/- mice (Gu et al., 2003). HSC/Ps from these mice showed normal short-term engraftment, but decreased adhesion, suggesting a key role for Rac2 in integrin-mediated stem-cell adhesion. In addition, Rac2-/- HSC/Ps formed colonies with both impaired growth and migration, and showed an increased rate of apoptosis.
In response to stromal derived factor 1, Rac2-/- cells failed in cortical F-actin assembly, and presented reduced cell spreading and actin-based membrane protrusion.
Role in neutrophils function
Several reports point out Rac2 is the predominant Rac GTPase functioning in neutrophils. These observations came from studies in neutrophils from Rac2-/- mice and a patient with a dominant-negative Rac2 mutation in which these cells showed decreased motility, adhesion, major defects in cortical F-actin assembly, and accordingly, chemotaxis and reduced phagocytosis and superoxide production by NAPH oxidase (Williams et al., 2000; Roberts et al., 1999; Li et al., 2002; Gu et al., 2003). Rac2 is required for oxidase activity through its direct interaction with p67-phox and cytochrome b 558.
Role in B-cell development
Rac2-/- mice exhibit multiple defects in B-cell development, with reduced numbers of peripheral blood B-cells and IgM-secreting plasma cells, a severe reduction in the number of marginal zone and peritoneal B1 cells (Croker et al., 2002). Rac2 participates in the positive selection through the B-cell receptor (BCR), since is activated by BCR cross-linking (Grill and Schrader, 2002).
Role in T-cell differentiation
Rac2 activity is required for interferon-gamma (IFNgamma) production both in vitro and in vivo during normal T-cell activation and Th1-cell differentiation, through simultaneous activation of both the NFkappaB and p38 pathways (Li et al., 2000).
Role in Mast cell survival
The absence of Rac2 results in defects growth, survival, chemotaxis, adhesion, and degranulation in mast cell (Yang et al., 2000). Rac2 is critical in regulating the growth factor-induced survival through activation of Akt and a change in expression levels of the Bcl-2 family members BAD and Bcl-XL (Yang et al., 2000).

Rac2 share significant sequence identity (~88%) with the other two members of the subfamily Rac: Rac1 and Rac3. The three proteins diverge primarily in the C-terminal 15 residues. Regarding to the biochemical properties, Rac2 shows a slower nucleotide association and is more efficiently activated by the Rac-GEF Tiam1 than Rac1 and Rac3.

POLYMORPHISMS
Two single nucleotide polymorphisms (SNP) have been observed in gliomas (Idbaih et al., 2008). The SNPs rs2239774 in exon 2 (codon 27, GCC to GCG, Ala to Ala) and rs3179967 in exon 6 (codon 159, GCT to GCC, Ala to Ala) were observed in 15/78 and 7/78 cases, respectively. No association between these two SNPs with phenotype, tumor grade, patient age, and patient gender was seen.

A point mutation has been identified in one allele of the Rac2 gene resulting in the substitution of Asp57 by an Asn (Rac2^D57N) in a patient with a primary immunodeficiency syndrome (Ambruso et al., 2000; Williams et al., 2000). Rac2^D57N binds GDP but not GTP and inhibits oxidase activation and superoxide production in vitro.

So far only two studies have searched for the presence of somatic mutations, both of them analyzed human brain tumors. Hwang et al. found 26% of cases had Rac2 gene mutation, two cases with decreased Rac2 expression and four cases with normal Rac2 expression. One case showed the mutation site nearby the GTP-binding site, which may affect Rac2 GTPase activity, but the site of Rac2 mutation seems not to concentrate in the effector region. However, Idbaih et al. did not find missense mutations in a series of 78 gliomas.