Protein: Ras-related C3 botulinum toxin substrate 1 (EC 3.6.5.2) (Cell migration-inducing gene 5 protein) (Ras-like protein TC25) (p21-Rac1) (P63000)
Organism: Homo sapiens (Human)
Function: 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. 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. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. 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. 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).
Subcellular location: Cell membrane {ECO:0000269|PubMed:1643658, ECO:0000269|PubMed:22843693, ECO:0000269|PubMed:29074776}; Lipid-anchor {ECO:0000269|PubMed:1903399}; Cytoplasmic side {ECO:0000269|PubMed:1643658, ECO:0000269|PubMed:19948726}. Melanosome {ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:21693584}. Cytoplasm {ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:29074776}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:P63001}. Cell projection, dendrite {ECO:0000250|UniProtKB:P63001}. Synapse {ECO:0000250|UniProtKB:Q6RUV5}. Nucleus {ECO:0000269|PubMed:12551911}. Note=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). {ECO:0000250|UniProtKB:P63001, ECO:0000250|UniProtKB:Q6RUV5, ECO:0000269|PubMed:12551911, ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:1903399}.
Interaction partners:
- Serine/threonine-protein kinase PAK 1
- Neutrophil cytosol factor 2
- Triple functional domain protein
- Rho GDP-dissociation inhibitor 1
- Arfaptin-2
- Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein
- Cytoplasmic FMR1-interacting protein 1
- Nck-associated protein 1
- Ras GTPase-activating-like protein IQGAP1
- Serine/threonine-protein kinase PAK 2
Sequence:
MQAIKCVVVGDGAVGKTCLLISYTTNAFPGEYIPTVFDNYSANVMVDGKPVNLGLWDTAGQEDYDRLRPLSYPQTDVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLRDDKDTIEKLKEKKLTPITYPQGLAMAKEIGAVKYLECSALTQRGLKTVFDEAIRAVLCPPPVKKRKRKCLLL