Rac1

Rac1, commonly written RAC1, is a small GTPase of the Rho family that acts as a molecular switch in signaling pathways that govern the organization of the actin cytoskeleton, cell migration, and vesicular trafficking. The protein is encoded by the RAC1 gene in humans and is highly conserved across eukaryotes.

Rac1 cycles between an inactive GDP-bound form and an active GTP-bound form. Guanine nucleotide exchange factors (GEFs) stimulate the exchange of GDP for GTP, while GTPase-activating proteins (GAPs) accelerate GTP hydrolysis. In its GTP-bound state, Rac1 interacts with downstream effectors such as PAK kinases and the WAVE regulatory complex to promote actin polymerization via the Arp2/3 complex, driving lamellipodium formation and cell movement. Rac1 also influences reactive oxygen species production through NADPH oxidase complexes in phagocytes and participates in endocytosis and vesicular trafficking.

Rac1 localization to membranes is driven by C-terminal prenylation (geranylgeranylation) and other post-translational modifications. The gene gives rise to multiple isoforms, including RAC1 and RAC1B from alternative splicing; RAC1B contains an insertion that can alter signaling outcomes.

Aberrant Rac1 signaling or mutations can contribute to disease. In cancer, RAC1 activity is linked to increased cell motility and metastasis, and specific mutations such as RAC1 P29S have been reported in melanoma. Researchers study Rac1 inhibitors that disrupt GEF–GTPase interactions or effector binding, as potential therapeutic approaches.