RAC1

The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

Rac Family Small GTPase 1

Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles (PubMed:1643658, PubMed:28886345).
Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity (PubMed:9121475).
In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts (PubMed:1643658).
In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. Required for atypical chemokine receptor ACKR2-induced LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In neurons, is involved in dendritic spine formation and synaptic plasticity (By similarity).
In hippocampal neurons, involved in spine morphogenesis and synapse formation, through local activation at synapses by guanine nucleotide exchange factors (GEFs), such as ARHGEF6/ARHGEF7/PIX (PubMed:12695502).
In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3. In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization (By similarity).
Isoform B
Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins (PubMed:14625275).
It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction (PubMed:14625275).

Biological Process actin cytoskeleton organizationManual Assertion Based On ExperimentIGI:MGI
Biological Process actin filament organizationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process actin filament polymerizationManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process anatomical structure morphogenesisManual Assertion Based On ExperimentTAS:ProtInc
Biological Process cell adhesionManual Assertion Based On ExperimentTAS:ProtInc
Biological Process cell migrationManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process cell motilityManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process cell projection assemblyManual Assertion Based On ExperimentIBA:GO_Central
Biological Process cell-matrix adhesion1 PublicationNAS:BHF-UCL
Biological Process cortical cytoskeleton organizationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process engulfment of apoptotic cellManual Assertion Based On ExperimentIBA:GO_Central
Biological Process establishment or maintenance of cell polarityManual Assertion Based On ExperimentIBA:GO_Central
Biological Process hepatocyte growth factor receptor signaling pathwayManual Assertion Based On ExperimentIMP:CAFA
Biological Process inflammatory responseManual Assertion Based On ExperimentTAS:ProtInc
Biological Process intracellular signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Biological Process lamellipodium assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process localization within membraneManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process motor neuron axon guidanceManual Assertion Based On ExperimentIBA:GO_Central
Biological Process negative regulation of fibroblast migrationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of interleukin-23 productionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of receptor-mediated endocytosisManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process neuron migrationISS:UniProtKB
Biological Process positive regulation of cell-substrate adhesionManual Assertion Based On ExperimentIGI:UniProtKB
Biological Process positive regulation of endothelial cell migrationManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of focal adhesion assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of lamellipodium assemblyManual Assertion Based On ExperimentIDA:MGI
Biological Process positive regulation of microtubule polymerizationManual Assertion Based On ExperimentIMP:CAFA
Biological Process positive regulation of neutrophil chemotaxisManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of protein phosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of Rho protein signal transductionManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process positive regulation of stress fiber assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of substrate adhesion-dependent cell spreadingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process Rac protein signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of actin cytoskeleton organizationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of cell shapeManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of cell sizeManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of hydrogen peroxide metabolic processManual Assertion Based On ExperimentTAS:BHF-UCL
Biological Process regulation of lamellipodium assemblyManual Assertion Based On ExperimentIGI:CAFA
Biological Process regulation of neutrophil migrationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of nitric oxide biosynthetic processISS:ARUK-UCL
Biological Process regulation of respiratory burstManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process regulation of stress fiber assemblyManual Assertion Based On ExperimentIGI:CAFA
Biological Process respiratory burst1 PublicationIC:ComplexPortal
Biological Process response to woundingManual Assertion Based On ExperimentTAS:ProtInc
Biological Process ruffle assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process ruffle organizationManual Assertion Based On ExperimentIDA:MGI
Biological Process semaphorin-plexin signaling pathwayISS:UniProtKB
Biological Process small GTPase mediated signal transductionManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process sphingosine-1-phosphate receptor signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process substrate adhesion-dependent cell spreadingManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process Wnt signaling pathway, planar cell polarity pathway1 PublicationNAS:ParkinsonsUK-UCL

Cell membrane
Melanosome
Cytoplasm
Cell projection, lamellipodium
Cell projection, dendrite
Synapse
Nucleus
Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine (PubMed:1903399).
Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:17081065).
Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts. Localizes to the lamellipodium in a SH3RF1-dependent manner (By similarity).
In macrophages, cytoplasmic location increases upon CSF1 stimulation (By similarity).
Activation by GTP-binding promotes nuclear localization (PubMed:12551911).

Intellectual developmental disorder, autosomal dominant 48 (MRD48):
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD48 patients manifest global developmental delay and moderate to severe intellectual disability.

GTP-bound active form is ubiquitinated by HACE1, leading to its degradation by the proteasome.
(Microbial infection) AMPylation at Tyr-32 and Thr-35 are mediated by bacterial enzymes in case of infection by H.somnus and V.parahaemolyticus, respectively. AMPylation occurs in the effector region and leads to inactivation of the GTPase activity by preventing the interaction with downstream effectors, thereby inhibiting actin assembly in infected cells. It is unclear whether some human enzyme mediates AMPylation; FICD has such ability in vitro but additional experiments remain to be done to confirm results in vivo.
(Microbial infection) Glycosylated at Tyr-32 by Photorhabdus asymbiotica toxin PAU_02230. Mono-O-GlcNAcylation by PAU_02230 inhibits downstream signaling by an impaired interaction with diverse regulator and effector proteins of Rac and leads to actin disassembly.
(Microbial infection) Glucosylated at Thr-35 by C.difficile toxins TcdA and TcdB in the colonic epithelium, and by P.sordellii toxin TcsL in the vascular endothelium (PubMed:7777059, PubMed:7775453, PubMed:8626575, PubMed:19744486, PubMed:24905543).
Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption and cell death, resulting in the loss of colonic epithelial barrier function (PubMed:7777059, PubMed:7775453).
(Microbial infection) Glycosylated (O-GlcNAcylated) at Thr-35 by C.novyi toxin TcdA (PubMed:8810274).
O-GlcNAcylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption (PubMed:8810274).
(Microbial infection) Palmitoylated by the N-epsilon-fatty acyltransferase F2 chain of V.cholerae toxin RtxA (PubMed:29074776).
Palmitoylation inhibits activation by guanine nucleotide exchange factors (GEFs), preventing Rho GTPase signaling (PubMed:29074776).