Vav 3 Oncogene (VAV3) Recombinant Protein

This gene is a member of the VAV gene family. The VAV proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases that activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. This gene product acts as a GEF preferentially for RhoG, RhoA, and to a lesser extent, RAC1, and it associates maximally with the nucleotide-free states of these GTPases. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

VAV3: a guanine nucleotide exchange factor (GEF) that activates RhoA, RhoG and, to a lesser extent, Rac1. Binds physically to the nucleotide-free states of those GTPases. Plays an important role in angiogenesis. Its recruitment by activated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly. May be important for integrin-mediated signaling, at least in some cell types. In osteoclasts, along with SYK tyrosine kinase, required for signaling through integrin alpha-v/beta-1 (ITAGV-ITGB1), a crucial event for osteoclast proper cytoskeleton organization and function. This signaling pathway involves RAC1, but not RHO, activation. Necessary for proper wound healing. In the course of wound healing, required for the phagocytotic cup formation preceding macrophage phagocytosis of apoptotic neutrophils. Responsible for integrin beta-2 (ITGB2)-mediated macrophage adhesion and, to a lesser extent, contributes to beta-3 (ITGB3)-mediated adhesion. Does not affect integrin beta-1 (ITGB1)-mediated adhesion. Interacts with the PH domain of APS. Interacts (via SH2 domains) with the phosphorylated form of EPHA2. Interacts with ROS1; constitutive interaction that mediates VAV3 phosphorylation. Down-regulated by EGF and TGF-beta. Four isoforms of the human protein are produced by alternative promoter. Isoform 1 and isoform 3 are widely expressed; both are expressed at very low levels in skeletal muscle. In keratinocytes, isoform 1 is less abundant than isoform 3. Isoform 3 is detected at very low levels, if any, in adrenal gland, bone marrow, spleen, fetal brain and spinal chord; in these tissues, isoform 1 is readily detectable.

Protein type: GEFs, Rac/Rho; GEFs; Nuclear receptor co-regulator; Motility/polarity/chemotaxis; Adaptor/scaffold; Actin-binding

Chromosomal Location of Human Ortholog: 1p13.3

Cellular Component: plasma membrane; cytosol

Molecular Function: protein binding; SH3/SH2 adaptor activity; metal ion binding; guanyl-nucleotide exchange factor activity; Rac guanyl-nucleotide exchange factor activity; GTPase activator activity; epidermal growth factor receptor binding

Biological Process: response to drug; integrin-mediated signaling pathway; lamellipodium biogenesis; neutrophil chemotaxis; axon guidance; platelet activation; positive regulation of cell adhesion; nerve growth factor receptor signaling pathway; positive regulation of signal transduction; positive regulation of apoptosis; positive regulation of phosphoinositide 3-kinase activity; vesicle fusion; regulation of small GTPase mediated signal transduction; B cell receptor signaling pathway; small GTPase mediated signal transduction; ephrin receptor signaling pathway; positive regulation of B cell proliferation; innate immune response; angiogenesis; vascular endothelial growth factor receptor signaling pathway; blood coagulation; response to DNA damage stimulus