Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol RAC1 contributors: mct/shn - updated : 22-05-2017
HGNC name ras-related C3 botulinum toxin substrate 1 (Rho family, small GTP binding protein Rac1)
HGNC id 9801
Corresponding disease
MCACCH microcephaly, cerebellar abnormalities, corpus callosum hypoplasia
Location 7p22.1      Physical location : 6.414.125 - 6.443.597
Synonym name
  • ras-like protein TC25
  • migration-inducing gene 5
  • cell migration-inducing gene 5 protein
  • rho family, small GTP binding protein Rac1
  • ras-related C3 botulinum toxin substrate 1
  • Synonym symbol(s) TC25, MIG5, TC-25, p21-Rac1, MGC111543
    DNA
    TYPE functioning gene
    STRUCTURE 29.47 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    text structure
  • lacking TATA and CAAT boxes
  • containing a CpG island surrounding the transcription initiation sites, and being GC rich, all characteristics of a housekeeping gene
  • MAPPING cloned Y linked N status confirmed
    Map pter - D7S2201 - D7S481 - RAC1 - D7S2553 - D7S2514 - cen
    Physical map
    PMS2 7p22 PMS2 postmeiotic segregation increased 2 (S. cerevisiae) RAC1 7p22 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) JTV1 7p22 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) LOC221955 7p22.2 KCCR13L HRI 7p22 heme-regulated initiation factor 2-alpha kinase KDELR2 7p22-p21 KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2 FLJ20306 7p22.2 hypothetical protein FLJ20306 LOC392861 7 similar to ribosomal protein L31 LOC392862 7 similar to GluR-delta2 philic-protein USP42 7p22.2 ubiquitin specific protease 42 PIK3CG 7q21.11 phosphoinositide-3-kinase, catalytic, gamma polypeptide PSCD3 7q21 pleckstrin homology, Sec7 and coiled-coil domains 3 ZDHHC4 7p22.2 zinc finger, DHHC domain containing 4 C7orf26 7p22.1 chromosome 7 open reading frame 26 LOC392626 7 similar to zinc finger protein 316; kruppel-related zinc finger protein; transcription factor MZF-3 LOC392627 7 LOC392627 PRKAR2B 7q22-q31.1 protein kinase, cAMP-dependent, regulatory, type II, beta ZNF325 7p22.2 zinc finger protein 325 MGC12966 7p22.2 hypothetical protein MGC12966 LOC392628 7 hypothetical gene supported by AB116525; NM_000535 RAC1 7p22 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) LOC221955 7p22.2 KCCR13L C7orf28B 7p22.2 chromosome 7 open reading frame 28B HBP1 7q22-q31 HMG-box transcription factor 1 LOC392863 7 similar to olfactory receptor MOR145-1 COG5 7q31 component of oligomeric golgi complex 5 KDELR2 7p22-p21 KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2 LOC392629 7 similar to unc-93 homolog B1; unc93 (C.elegans) homolog B; unc-93 related protein LOC392864 7 hypothetical gene supported by AK122996 FLJ20306 7p22.2 hypothetical protein FLJ20306 LOC391999 7 similar to ribosomal protein L31 LOC340265 7p22.2 similar to GluR-delta2 philic-protein LOC392865 7 similar to Asparagine-linked glycosylation 1 homolog (yeast, beta-1,4-mannosyltransferase) LOC392866 7 similar to hypothetical protein FLJ10661 ZDHHC4 7p22.2 zinc finger, DHHC domain containing 4 C7orf26 7p22.1 chromosome 7 open reading frame 26 LOC389461 7 similar to zinc finger protein 316; kruppel-related zinc finger protein; transcription factor MZF-3
    RNA
    TRANSCRIPTS type messenger
    text several alternatively spliced transcript variants
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 2341 25 192 ubiquitously expressed in all tissues 2000 11062023
  • having a 57 bp in-frame deletion of exon 3b in the coding region
  • lacking exon 4 and encoding the shorter RAC1 isoform
  • 7 splicing 2398 25 211 . skin and epithelial tissues from intestine tract . elevated in colorectal tumors at various stages of neoplatic progression . upregulated in colon and breast cancer cells 2008 18319303
  • RAC1B
  • including the alternatively spliced 57 bp region (exon 3b) that is missing in transcript variant RAC1
  • cannot induce junction disassembly
  • PAK1 cannot be activated by RAC1B, suggesting that this may contribute to the inability of RAC1B to disrupt cell-cell contacts in keratinocytes
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentepithelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text
  • RAC1 and neuron-specific RAC3 GTPases are coexpressed in the developing mammalian brain
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • C terminal consensus sequence (CXXX) which localizes RAS to the inner plasma membrane, C-terminal polybasic region (PBR)
  • conjugated LipoP , Other
    HOMOLOGY
    interspecies ortholog to rac1, danio rerio
    ortholog to Rac1, Mus musculus
    ortholog to Rac1, Rattus norvegicus
    intraspecies homolog to RAC2, RAC3
    Homologene
    FAMILY
  • cognate Rho family G protein
  • CATEGORY signaling , receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    text inner surface of plasma membrane
    basic FUNCTION
  • playing a significant role in the bone resorptive activity of cells, probably by regulating the motility of osteoclasts
  • has a known role in cerebellar development
  • potent activator of mineralocorticoid receptor signal transduction
  • involved in the production of superoxide in neutrophils
  • putative regulator of mitogen-induced cytoskeletal changes essential for membrane ruffling and C-jun aminoterminal kinase JNK
  • regulator of actin filament at the plasma membrane to produce lamellipodia and membrane ruffles, controlling proliferation, adhesion, migration during embryonic development
  • key downstream target in Ras signaling
  • linking growth factor receptor to the activator of actin polymerization
  • activating JNK signaling pathway
  • reduction of oxygen to O-2 at the expense of NADPH, the O2-generated is the precursor of potent oxidants used to kill the invading microorganisms
  • exerting its effects in the epidermis by negatively regulating c-Myc through p21-activated kinase 2 (PAK2) phosphorylation
  • may playing an important role in corneal wound healing
  • have distinct roles in regulating cell morphology, migration and invasion, but are not essential for macrophage migration or chemotaxis
  • critically involved in M-CSF receptor signaling and mediates survival signaling primarily through PI3K/Akt pathways
  • regulating cell adhesion, migration and differentiation in various cell types
  • role in hematopoietic development and function
  • critical role in B cell development and signaling
  • controles the formation of dendrites in mature dendritic cells, their polarized short-range migration toward T cells, and T cell priming
  • critical for the hypertrophic response in the heart
  • negatively controls LPS-induced IL-23 p19 expression through an NF-kappaB p65 trans activation-dependent
  • mediator of colony-stimulating factor 1 (CSF-1)-dependent actin remodeling in osteoclasts
  • central role for Rac1 in the control of NDRG1-induced breast cancer cell-cycle progression and proliferation through up-regulating the expression of cyclin D1 and CDKN1A
  • essential player for mediating the induction of cyclin D1 and CDKN1A by HRG in breast cancer cells
  • involved in endothelial cell cytoskeletal reorganization and in neovessel formation
  • shares with RAC3 the ability to interfere with cadherin-mediated adhesion
  • both RAC1 and RAC3 are important for the development of the nervous system, wherein they play complementary roles during late stages of neuronal and brain development
  • its overexpression contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression
  • with RHOA, and RHOB, are involved in the establishment of the migratory and invasive phenotype of tumour cells that have CDH1 mutation
  • play essential roles in coordinating directional migration and superoxide production during neutrophil responses to chemoattractants
  • RAC1 and RAC2 GTPases are essential for normal bone marrow erythropoiesis but that they are dispensable for erythropoiesis in the spleen, implying different signaling pathways for homeostatic and stress erythropoiesis
  • critical regulator of both MTOR and CRTC2 in response to growth-factor stimulation
  • role for neuronal RAC1 and RAC3 in dictating proper lymphoid organ development, suggesting the existence of lymphoid-extrinsic mechanisms linking neural defects to the loss of immune-competence
  • RAC1 and RAC3 GTPases participate in the normal development of hilar mossy cells, and indicate that they are involved in the regulation of the migration of the mossy cell precursor by preventing their arrival to the dorsal hilus
  • cell-autonomous and stage-specific functions for the small Rho GTPases CDC42 and RAC1 in the course of adult hippocampal neurogenesis
  • RAC1 and CDC42 are molecular switches that control many cellular processes, but are best known for their roles in the regulation of actin cytoskeleton dynamics
  • divergent roles of RAC1 and CDC42 function in podocyte maintenance and injury
  • FHOD1 and the small GTPase RAC1 promote vaccinia virus actin-based motility (PMId: 24062339)
  • RAC1 has been reported to function downstream of ARF6 to control membrane ruffling and cell migration
  • RAC1 controls surface mobilization of CD40LG on activated platelets and MMP9 secretion from neutrophils
  • RHOA and RAC1 function as master regulators of cytokinesis by controlling the actomyosin cytoskeleton
  • importance of RAC1 in neuronal development
  • CELLULAR PROCESS cell cycle
    cell communication
    PHYSIOLOGICAL PROCESS
    text
  • cell cycle progression through G1 to S
  • cytoskeletal rearrangements during phagocytosis and cell motility in the late steps of the apoptotic process (complementation group 2 in C elegans)
  • PATHWAY
    metabolism
    signaling signal transduction
  • PI3K/Akt pathways
  • CCL2/RAC1/PI3K pathway plays critical role in resolution of acute lung inflammation
  • RAC1-dependent signalling pathway that, through Nedd4-mediated ubiquitylation of DVL1, stimulates the maturation of epithelial cell-cell contacts
  • a component
  • component of NADPH oxidase system cypb245
  • prenylation
  • RAP1GDS1-RAC1 complexes accumulate in the nucleus
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • GTP
  • protein
  • POR1
  • Nef-associated kinase
  • guanine nucleotide dissociation inhibitor, GDI
  • T-lymphoma invasion and metastasis factor 1, Tiam1
  • with KRAS and RHoA, bind to RAP1GDS1 in both active and inactive forms which requires the presence of poly-basic residues in the C-termini of the GTPases
  • TRE17
  • insulin receptor substrate (IRS) p53, IRSp53
  • CDC42, WAS to the cytoskeletal regulation of B lymphocytes
  • interaction with FLNB, a scaffolding protein connecting also VAV2and KDR proteins for endothelial cell motility
  • interaction between full-length MTSS1L and RAC1 is implicated in membrane deformation and subjected to a growth factor-mediated regulation through the C-terminal sequence
  • (SUMO) E3-ligase, PIAS3
  • OBSCN is a specific activator of RHOQ but not the Rho GTPases RAC1 and CDC42
  • RAC1 and RAC3 interact with GIT1, a multifunctional Arf-GAP protein, which regulates cell-matrix adhesion, cell spreading and endocytosis
  • CGNL1 is a regulator of the activity of two small GTPases, RAC1 and RHOA, through the functional interaction with their respective activators, TIAM1 and ARHGEF2
  • binding of RAC1 to MTOR does not depend on the GTP-bound state of RAC1, but on the integrity of its C-terminal domain
  • interaction between LRRK2 and the Rho GTPase, RAC1, which plays a critical role in actin cytoskeleton remodeling necessary for the maintenance of neurite morphology
  • SH3BP1 downregulates RAC1 at the motile-cell front, indicating that RAC1 inactivation in this location, as well as its activation by GEF proteins, is a fundamental requirement for cell motility
  • EHD2 regulates trafficking from the plasma membrane by controlling RAC1 activity
  • RHOC, and RAC1 are essential, for IGFBP1-induced extravillous trophoblast (EVT migration
  • CRB3 and the RAC1-PI3K module are antagonists, and the fine balance between the activities of these proteins is crucial to maintain epithelial organization and an appropriate apical to basolateral ratio
  • SSX2IP mediates the activation of RAC1 through VAV2
  • role of the HACE1 E3 ubiquitin-ligase in controlling RAC1 ubiquitylation and activity
  • PARD3 regulates RAC1 activation by BDNF but not by NRG1-Type III in Schwann cells, although both ligands activate RAC1
  • OPHN1 exhibits strong GTPase-stimulating activity towards RHOA, CDC42, and RAC1 and regulates cell adhesion and spreading
  • BECN1 bound to RAC1, recruited to early phagocytotic cups, and required for apoptotic cell internalization
  • regulates cell migration and cell-cell adhesion through RAC1 (
  • interaction with NEDD4, that requires the hypervariable C-terminal domain of RAC1 and the WW domains of NEDD4
  • HDAC3-RAC1 interaction, but not HDAC3 activity, is necessary for down-regulation of HDAC2 by RAC1
  • upon clustering of ICAM1, the Rho-guanine nucleotide exchange factor TRIO activates RAC1, prior to activating RHOG, in a filamin-dependent manner
  • RIN2 connects three GTPases, RRAS, RAB5A and RAC1, to promote endothelial cell adhesion through the regulation of integrin internalization and RAC1 activation
  • TNFAIP8L2 binds to the C terminus of RAC1 suggesting that it may regulate membrane translocation of RAC1
  • crucial role of S100A10 in actin dynamics promoting cell spreading via RAC1 activation
  • CD81-RAC1 interaction was direct and independent of RAC1 activation status (interaction of RAC1 with the C-terminal cytoplasmic domain of CD81 is a novel regulatory mechanism of the GTPase activity turnover)
  • PLXNB1 binds in a GTP-dependent manner to RAC1, RAC2, RAC3, RND1, RND2, RND3, and RHOD
  • FHOD1 is activated by the small GTPase RAC1, RAC1 was enriched and activated at the membrane surrounding actin tails
  • GRIN3A binds GIT1, a postsynaptic scaffold that assembles actin regulatory complexes, including the RAC1 guanine nucleotide exchange factor ARHGEF7, to promote RAC1 activation in spines
  • RACGAP1 negatively controls the activity of RAC1 and CDC42, which are key molecular switches acting on the microtubule and actin cytoskeleton and controlling various cell processes such as proliferation, adhesion and motility
  • NCK1-ELMO1 interaction promoting RAC1 activation and cell motility
  • serine/threonine protein kinase AKT2 is critically involved in insulin-dependent RAC1 activation
  • NAV1 interacts and colocalizes with TRIO, a Rho guanine nucleotide exchange factor that enables neurite outgrowth by activating the Rho GTPases RAC1 and RHOG
  • PLEKHG4 regulates RAC1 downstream of AKT2, leading to the stimulation of glucose uptake in skeletal muscle
  • RCC2, attenuates RAC1 activation outside the protrusive tip by binding to the RAC1 switch regions and competitively inhibiting GEF action, thus preventing off-axial protrusion
  • ARHGEF7 and GIT1 are required for synaptic GABA(A)R surface stability through the activity of the GTPase RAC1 and downstream effector PAK1
  • TRIO is a mitotic GEF of RAC1, and TRIO controls RAC1 activation and subsequent F-actin remodeling in dividing cells
  • PICK1 binds RAC1 and CDC42, via distinct but overlapping binding sites
  • to activate RAC1 and consequently PYGM, PRKCQ phosphorylates ARHGEF6 in T cells
  • importance of spatio-temporal regulation of the actin cytoskeleton through TRIO and RAC1 at CDH5-based cell-cell junctions in the maintenance of the endothelial barrier
  • CSNK2A1 interacts at the neuromuscular synapse with RPSN, RAC1, YWHAG, and DOK7 proteins and phosphorylates the latter two
  • role for RALA downstream of RAC1 in skeletal muscle insulin signalling
  • RAC1 initiates its own inactivation by decreasing PREX2 GEF activity
  • MARCKS upregulation increases VSMC motility by activation of RAC1 and CDC42
  • assembles with multiple members of the WASL complex and the RhoGTPase RAC1 and modulates their activity
  • RAB23 promotes squamous cell carcinoma cells migration and invasion by regulating ITGB1/TIAM1/RAC1 pathway
  • RAB23 serves as an important oncoprotein in human astrocytoma by regulating cell invasion and migration through RAC1 activity
  • HACE1 controls cell proliferation and ubiquitylates the small GTPase RAC1 to target it to proteasomal degradation
  • SH3BP1 specifically inactivating RAC1 and its target WASF2 is required for cell motility, thus regarded as an essential regulator of cancer cell metastasis
  • causal relationship between increased RAC1/CFL1 signaling, synaptic defects, and impaired sensory processing in FRAXA and role for impaired RAC1/CFL1 signaling in the aberrant spine morphology and spine density associated with FRAXA
  • cell & other
  • low-density cholesterol-rich membranes
  • REGULATION
    activated by
  • CRKA (CRKII) and DOCK1
  • affixin via ARHGEF7
  • Nef-associated kinase
  • bFGF- and NGF-induced phosphorylation of p85 betaPIX
  • Caveolin-1, CAV1
  • repressed by SH3BP1
    Other
  • down-regulated by estrogen
  • phosphorylated by Akt protein kinase
  • ASSOCIATED DISORDERS
    corresponding disease(s) MCACCH
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colorectal cancer
    tumoral     --over  
    in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells
    tumoral somatic mutation      
    in melanoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneous  
    therapeutic target for chronic kidney disease
    cardiovascularcardiomyopathy 
    therapies which target myocardial RAC1 may be beneficial in the treatment of cardiac hypertrophy
    cancerskin 
    pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit
    ANIMAL & CELL MODELS
  • deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow
  • mice with specific Rac1 deficiency in the B cell lineage display a completely blocked development of B cell
  • deletion of Rac1 in adult mouse epidermis stimulated stem cells to divide and undergo terminal differentiation, leading to failure to maintain the interfollicular epidermis, hair follicles, and sebaceous glands
  • temporally and specifically deleted Rac1 gene in adult mouse cardiomyocytes leads to decreased gp91(phox) and p67(phox) interaction, NADPH oxidase activity, and myocardial oxidative stress in response to angiotensin II stimulation
  • amount of Rac1 associating with beta4 integrin and the activity of both Rac1 and cofilin are significantly lower in BPAG1e-deficient keratinocyte cells