Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2)(RAC2) ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2)(RAC2) Related Genes Homo sapiens
CYTOBAND 22q13.1,
GENERIF_SUMMARY Interaction between p21-activated protein kinase and Rac during differentiation of HL-60 human promyelocytic leukemia cell, Rac2 is activated via a T cell receptor/DOCK2 signal transduction pathway that activates IL-2 transcription in Jurkat cells, dissociations of Rac1 and Rac2 from LyGDI enable the PI 3-kinase-dependent translocations of Rac GTPases to the plasma membrane, Rac2 does not have the same role as Rac1 in the human NADPH oxidase complex, in neutrophils, Rac2 and Cdc42 are involved in FcR- and CR3-induced activation and for properly functioning signal transduction involved in the generation of oxygen radicals., Our results showed a low frequency of mutation and no hot spots of mutation in Rac2 gene in brain tumors, suggesting a decreased possibility of Rac2 in the brain tumorigenesis., diminished rho family, small GTP-binding protein Rac2(Rac2) expression in cord blood neutrophils may contribute to the defects observed in cord blood neutrophil function, Rac1 and Rac2 have distinct roles in regulating cell morphology, migration and invasion, but are not essential for macrophage migration or chemotaxis., Endogenous P-Rex1 translocates to areas of Rac2 and cytoskeletal activation at the leading edge in response to chemoattractant stimuli in human neutrophils and that this translocation can be negatively modulated by activation of PKA and by cell adhesion., RACK1 amd Rac2 are components of complexes involved in NK cell homotypic adhesion., These results provide evidence that the activation of Rac2 by angiotensin II is exerted through multiple signalling pathways, involving Ca(2)(+)/calcineurin and protein kinases., In primary activated CD4(+) T cells, Rac1 and Rac2 were independently required for maximal TCR-induced apoptosis., DOCK2 and DOCK9 specifically recognize Rac2 and Cdc42 through their switch 1 as well as beta2-beta3 regions and the mode of recognition via switch 1 appears to be conserved among diverse Rac-specific DHR-2 GEFs, RAC2 is rarely mutated in gliomas, PI3K and Src-ELMO-Dock2 pathways work in parallel to activate Rac2 and modulate chemotaxis in response to a CXCL8 gradient in neutrophils., important in T cell immunological synapse assembly, Primary granule exocytosis in human neutrophils is regulated by Rac2-dependent actin remodeling., OAG-induced NOX2 activation was mediated by PKC and PI3K through the regulation of Rac2 activity, Rac1 and Rac2 are both required for efficient chemotaxis., Human neutrophils kill invading microbes while limiting oxidative damage to the adjacent surrounding healthy tissue through differential activation of Rac1 and Rac2 in response to different concentrations of chemoattractant., Data show that activation of PLCbeta(2) by alpha(q) and beta1gamma2 differ from activation by Rac2 and from each other., Rac1 and Rac2 GTPases are essential for normal bone marrow erythropoiesis, but they are dispensable for erythropoiesis in the spleen., Mutations in RAC2 GTPase have been found to cause a human disease, a severe phagocytic immunodeficiency characterized by lifethreatening infections in infancy. Review., LFA-1-induced stabilization of ARE-containing mRNAs in T cells is dependent on HuR, and occurs through the Vav-1, Rac1/2, MKK3 and p38MAPK signaling cascade, activated cells PLD2 affects Rac2 in an initial positive feedback, but as Rac2-GTP accumulates in the cell, this constitutes a "termination signal" leading to PLD2 inactivation., data reinforce recent evidences that susceptibility alleles/haplotypes are shared among multiple autoimmune disorders and support a causal role for RAC2 variants in the pathogenesis of autoimmune diseases., This variant reduced binding of the NCF2 gene product p67(phox) to RAC2. This study found a novel genetic association of RAC2 with Crohn's disease (CD) and replicated the previously reported association of NCF4 with ileal CD., The mRNA and protein levels of Rac1 and Rac2 are elevated following exposure of endothelial progenitor cells to the chemokine SDF-1alpha., CNF1 modified Rac2, which then interacted with the innate immune adaptors IMD and Rip1-Rip2 in flies and mammalian cells, respectively, to drive an immune response, Rac2 GTPase alters mitochondrial membrane potential and electron flow through the mitochondrial respiratory chain complex III, generating high levels of reactive oxygen species in chronic-phase CML stem cells and primitive leukemia progenitor cells., study identified several missense mutations for RAC1 and RAC2, with some of the mutant proteins, including RAC1(P29S), RAC1(C157Y), RAC2(P29L), and RAC2(P29Q), being found to be activated and transforming; activating mutations of RAC GTPases were thus found in a wide variety of cancers at a low frequency, findings indicate that a chemokine-controlled pathway, consisting of Galphai2, ELMO1/Dock180, Rac1 and Rac2, regulates the actin cytoskeleton during breast cancer metastasis, Mutations in hematopoiesis-specific Rho GTPases Rac2 and RhoH lead to a wide range of human blood disorders. (Review), p47(phox) and Rac2 accumulate only transiently at the phagosome at the onset of NADPH activity and detach from the phagosome before the end of reactive oxygen species production., These studies imply functional importance of iNOS and its interaction with Rac2 in pathogen killing by the neutrophils., homozygous loss-of-function RAC2 mutation in 2 patients with early-onset and progressive hypogammaglobulinemia(novel homozygous nonsense mutation in codon 56 (W56X)of RAC2 gene), our present analysis reinforces the involvement in ACT of the regulatory NADPH oxidase subunit RAC2 gene variant rs13058338 and, to a lesser extent of the CYBA gene variant rs4673., RAC2 specifically interacted with a set of mitochondrial proteins., RAC1/RAC2 and SFK are proximal and essential for phosphatidylinositol 3-kinase (PI3K) activation in NK cell-mediated direct cytotoxicity against Cryptococcus neoformans.,
OMIM_DISEASE Neutrophil immunodeficiency syndrome,
SP_COMMENT disease:Defects in RAC2 are the cause of neutrophil immunodeficiency syndrome [MIM:608203]., enzyme regulation:Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase., function:Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as secretory processes, phagocytose of apoptotic cells and epithelial cell polarization. Seems to be involved in the regulation of the NADPH oxidase., online information:RAC2 mutation db, similarity:Belongs to the small GTPase superfamily. Rho family., subcellular location:Membrane-associated when activated., subunit:Interacts with DOCK2, which may activate it., tissue specificity:Hematopoietic specific.,