BioPAX pathway converted from "Activation of Rac1 by FARP2" in the Reactome database.LEFT-TO-RIGHTActivation of Rac1 by FARP2Sema3A-mediated dissociation of FARP2 from Plexin-A is followed by activation of Rac1 by the GEF activity of released FARP2.<br>FARP2 is critical for Sema3A-mediated axonal repulsion through two independent downstream signaling pathways. Sema3A mediated disassociation of FARP2 from Plexin-A is followed by activation of Rac by GEF activity of released FARP2, binding of Rnd1 to plexin-A and down regulation of R-Ras by GAP activity of plexin-A.Authored: Garapati, P V, 2009-03-23 09:59:28Reviewed: Kumanogoh, A, Kikutani, H, 2009-09-01Edited: Garapati, P V, 2009-03-23 10:00:07GTPGuanosine 5'-triphosphateReactome DB_ID: 29438cytosolGENE ONTOLOGYGO:0005829GTP [ChEBI:15996]GTPGuanosine 5'-triphosphateChEBICHEBI:15996Reactome Database ID Release 7529438Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29438ReactomeR-ALL-294383Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29438.3Reactomehttp://www.reactome.orgCOMPOUNDC00044additional informationMIMI:0361Rac1:GDPReactome DB_ID: 421113plasma membraneGENE ONTOLOGYGO:0005886Rac1Ras-related C3 botulinum toxin substrate 1RAC1_MOUSEReactome DB_ID: 421093UniProt:P63001 Rac1Rac1FUNCTION Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states (PubMed:24352656). 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 glioma cells, promotes cell migration and invasion. 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 podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. In neurons, is involved in dendritic spine formation and synaptic plasticity (PubMed:24352656, PubMed:26969129). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3.ACTIVITY 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. GTP hydrolysis is stimulated by ARHGAP30 and ARHGAP44.SUBUNIT Interacts with the GEF proteins PREX1, FARP1, FARP2, DOCK1, DOCK2 and DOCK7, which promote the exchange between GDP and GTP, and therefore activate it. Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization. Found in a trimeric complex composed of DOCK1 and ELMO1, which plays a central role in phagocytosis of apoptotic cells. Interacts with RALBP1 via its effector domain. Interacts with BAIAP2, BAIAP2L1, PLXNB1, CYFIP1/SRA-1 and DEF6. Probably found in a ternary complex composed of DSCAM, PAK1 and RAC1. Interacts with DSCAM; the interaction requires PAK1. Interacts with TBC1D2. Interacts with UNKL. Interacts with USP6. Interacts with SPATA13. Interacts with ITGB4. Interacts with the GTP-bound form of RAB7A. Interacts with ARHGEF2. Interacts with ARHGEF16; mediates activation of RAC1 by EPHA2. Interacts with NOXA1. Interacts with S100A8 and calprotectin (S100A8/9). Interacts with ARHGDIA; the interaction is induced by SEMA5A, mediated through PLXNB3 and inactivates and stabilizes RAC1. Interacts with PACSIN2. Interacts with ITGB1BP1 (By similarity). Interacts with the GEF protein RASGRF2, which promotes the exchange between GDP and GTP, and therefore activates it. Interacts with PARD6A, PARD6B and PARD6G in a GTP-dependent manner. Part of a complex with MAP2K3, MAP3K3 and CCM2. Interacts with NISCH. Interacts with PIP5K1A. Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. Interacts with SRGAP2. Interacts with PLXNB3. Interacts (when active) with PPP5C (via TPR repeats); activates PPP5C phosphatase activity and translocates PPP5C to the cell membrane. Interacts with RAPH1 (via Ras associating and PH domains) (By similarity). Interacts with MTSS2 (via IMD domain); this interaction may be important to potentiate PDGF-induced RAC1 activation. Interacts (GTP-bound form) with SH3RF3. Interacts with PAK2 (By similarity). Interacts (GTP-bound form) with SH3RF1 (PubMed:22959435). Found in a complex with SH3RF1, MAPK8IP1/JIP1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1 (PubMed:23963642). Interacts (both active GTP- or inactive GDP-bound forms) with SH3RF2 (By similarity). Interacts (GTP-bound form preferentially) with CYRIB (By similarity). Interacts with DOCK4 (via DOCKER domain); functions as a guanine nucleotide exchange factor (GEF) for RAC1 (By similarity). Interacts with GARRE1 (By similarity).TISSUE SPECIFICITY Widely expressed.DEVELOPMENTAL STAGE Expressed in the neocortical neurons in the developing brain.DOMAIN The effector region mediates interaction with DEF6.PTM GTP-bound active form is ubiquitinated by HACE1, leading to its degradation by the proteasome.DISRUPTION PHENOTYPE Conditional knockout of Rac1 in the telencephalic ventricular zone of embryos leads to primary microcephaly. Self-renewal, survival, and differentiation of telencephalic neural progenitor cells is affected.SIMILARITY Belongs to the small GTPase superfamily. Rho family.Mus musculusNCBI Taxonomy10090UniProtP630011EQUAL189EQUALReactome Database ID Release 75421093Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421093ReactomeR-MMU-4210932Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-421093.21GDPGuanosine 5'-diphosphateGuanosine diphosphateReactome DB_ID: 29420GDP [ChEBI:17552]GDPGuanosine 5'-diphosphateGuanosine diphosphateChEBICHEBI:17552Reactome Database ID Release 7529420Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29420ReactomeR-ALL-294202Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29420.2COMPOUNDC000351Reactome Database ID Release 75421113Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421113ReactomeR-MMU-4211132Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-421113.2Rac1-GTPReactome DB_ID: 42110311Reactome Database ID Release 75421103Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421103ReactomeR-MMU-4211031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-421103.1ACTIVATIONFARP2FERM, RhoGEF and pleckstrin domain-containing protein 2FARP2_MOUSEReactome DB_ID: 421077UniProt:Q91VS8 Farp2Farp2Kiaa0793FUNCTION Functions as guanine nucleotide exchange factor that activates RAC1. May have relatively low activity (PubMed:23375260 and PubMed:20702777). Plays a role in the response to class 3 semaphorins and remodeling of the actin cytoskeleton. Plays a role in TNFSF11-mediated osteoclast differentiation, especially in podosome rearrangement and reorganization of the actin cytoskeleton. Regulates the activation of ITGB3, integrin signaling and cell adhesion.SUBUNIT Interacts with PLXNA1. Interaction with PLXNA1 or PIP5K1C lowers its guanine nucleotide exchange activity. Dissociates from PLXNA1 when SEMA3A binds to the receptor. Interacts with PIP5K1C via its FERM domain. The interaction with PIP5K1C is enhanced by SEMA3A binding. Interacts with RAC1.TISSUE SPECIFICITY Detected in adult brain, lung and testis. Detected in embryonic hippocampus and brain cortex.INDUCTION Up-regulated by TNFSF11.DOMAIN Intramolecular interaction between the DH domain and the PH domains can stabilize the protein in an autoinhibited conformation.UniProtQ91VS81EQUAL1065EQUALReactome Database ID Release 75421077Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421077ReactomeR-MMU-4210771Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-421077.1GENE ONTOLOGYGO:0030676gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 75421141Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421141Reactome Database ID Release 75421147Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421147ReactomeR-MMU-4211471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-421147.116286926Pubmed2005FARP2 triggers signals for Sema3A-mediated axonal repulsionToyofuku, TYoshida, JSugimoto, TZhang, HKumanogoh, AtsushiHori, MKikutani, HitoshiNat Neurosci 8:1712-917607942Pubmed2007The CRMP family of proteins and their role in Sema3A signalingSchmidt, EFStrittmatter, SMAdv Exp Med Biol 600:1-11