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FLASH GENE
Symbol CDC42 contributors: mct - updated : 19-06-2018
HGNC name cell division cycle 42 (GTP binding protein, 25kDa)
HGNC id 1736
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • Cdc42/Rac Interactive Binding domain
    • HOMOLOGY
    interspecies homolog to yeast S.cerevisiae CDC42
    ortholog to cdc42, Danio rerio
    ortholog to CDC42, Pan troglodytes
    ortholog to Cdc42, rattus norvegicus
    Homologene
    FAMILY
  • GTP binding protein family
  • Rho/Rac subfamily, Ras-like GTPase
  • CCDC42 family
    • CATEGORY signaling , transport
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,granule
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    text
  • trans-Golgi network
  • localize to intracytosplasmic vesicles
  • localizes the exocyst to primary cilia, whereupon the exocyst targets and docks vesicles carrying ciliary proteins
    • basic FUNCTION
  • regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis and cell cycle progression
  • activating the Jun N-terminal kinase/stress activated protein kinase required for cell polarization
  • controlling endocytosis in dendritic cells
  • stimulating the actin-depolymerizing activity of WASL
  • promoting cell cycle progression from G1 to S
  • regulating in cooperation with WASP podosomeal adhesion structure in primary macrophages
  • controls the formation of actin bundle-containing filopodia at the cellular periphery
  • stimulating formation of filopodia
  • playing an important role for the establishment and maintenance of epithelial polarity
  • having an essential role in establishing the apical-basal polarity of the telencephalic neuroepithelium, which is needed for the expansion and bifurcation of cerebral hemispheres
  • playing a role as a regulator of E-cadherin down-regulation and intracellular trafficking and further acting as an important contributor to the invasive phenotype of breast cancer cells
  • crucial for differentiation of skin progenitor cells into hair follicles lineage and regulates the turnover of beta-catenin
  • has an essential role in establishing the apical-basal polarity of the telencephalic NE
  • roles of CDC42 signaling in amoeboid and mesenchymal movement and tumor cell invasion
  • required for the mechanism that orients the spindle parallel to the substratum in nonpolarized adherent cells
  • regulates both PtdIns(3,4,5)P3 and the actin cytoskeleton through PI(3)K- and p21-activated kinase 2 (PAK2)/âPix-signaling pathways, respectively
  • during wound-induced cell migration, the small G protein CDC42 acts through the polarity protein DLG1 to regulate the interaction of dynein with microtubules of the cell front
  • controls cell polarity in a wide variety of cellular contexts
  • controls vascular network assembly through PRKCI during embryonic vasculogenesis
  • controls the cholesterol-regulated transport and localization of NPC1L1, and plays a role in cholesterol absorption
  • required for the apical membrane localization of hepatic NPC1L1
  • pivotal regulator of polarity
  • physiological importance of CDC42, but not RAC1 or RHOA, in establishing podocyte architecture and glomerular function
  • implicated in RAS-driven tumor growth, suggesting that targeting CDC42 is beneficial in RAS-mediated malignancies
  • CDC42 plays an important role in trophoblast migration and is obligatory for EDN1 action
  • is essential for formation and maintenance of the respiratory tract during morphogenesis of the fetal lung
  • controls exocytic events during phagosome formation
  • 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
  • important role of CDC42 in host protection from lethal infections
  • concerted action of ARF1, ARHGAP21, and CDC42 to regulate fluid phase endocytosis
  • EPHB2, CDC42, and PAK3 are broadly capable of controlling dendritic spine formation and synaptic plasticity and are implicated in multiple cognitive disorders
  • CDC42/WASL/stress fibers/YAP1 signal pathway may potentially play an important role in regulating podocyte apoptosis
  • is a small Rho GTPase and key regulator of cytoskeletal components
  • important roles of CDC42 in bone modeling and remodeling
    • CELLULAR PROCESS cell cycle, checkpoint
    cell communication
    PHYSIOLOGICAL PROCESS endocytosis transport
    PATHWAY
    metabolism
    signaling
    a component
  • bound to COPG2 and the coatomer complex CDC42SE1
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • mitogen-activated protein kinase kinase kinase 4 (MAP3K4)
  • Wiskott-Aldrich syndrome (eczema-thrombocytopenia) (WASP)
  • neutrophil cytosolic factor 2 (NCF2 also known as P67PHOX)
  • Arp2/3 complex
  • neurogenic differentiation 1 (NEUROD1 also known as BETA2)
  • regulating the exit of apical and basolateral proteins from the trans-Golgi network
  • RAC1 and WAS to the cytoskeletal regulation of B lymphocytes
  • IQ motif containing GTPase activating protein 1 (IQGAP1)
  • IQ motif containing GTPase activating protein 2 (IQGAP2)
  • Rho GDP dissociation inhibitor (GDI) gamma (ARHGDIG)
  • Rho GDP dissociation inhibitor (GDI) alpha (RhoGDI)
  • BAI1-associated protein 2 (BAIAP2 also known as IRSP53)
  • BCL2/adenovirus E1B 19kDa interacting protein 2 (BNIP2)
  • centrosomal protein 250kDa (CEP2) and CDC42 effector protein (Rho GTPase binding) 5 (CEP5)
  • CDC42 effector protein (Rho GTPase binding) 5 (CDC42EP5 also known as Borg3)
  • CDC42 small effector 1 (CDC42SE1) and CDC42 small effector 1 (CDC42SE1)
  • Cdc42 GTPase-activating protein (CDGAP)
  • dedicator of cytokinesis 9 (DOCK9 also known as ZIZIMIN1)
  • mitogen-activated protein kinase kinase kinase 11 (MAP3K11)
  • guanine nucleotide exchange factor DBS
  • p21 protein (Cdc42/Rac)-activated kinase 4 (PAK4)
  • p21 protein (Cdc42/Rac)-activated kinase 6 (PAK6)
  • PAR6alpha, beta and gamma
  • phospholipase D1, phosphatidylcholine-specific (PLD1)
  • protein kinases Clambda and -zeta
  • ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2)
  • ras homolog gene family, member J (RHOJ also known as TCL)
  • TRE17 protein (TRE17)
  • ERBB receptor feedback inhibitor 1 (ERRFI1 also known as GENE-33 and MIG-6)
  • contactin 2 (axonal) (CNTN2 also known as TAX)
  • Rho GTPase activating protein 17 (ARHGAP17 also known as RICH-1)
  • formin binding protein 1-like (FNBP1L also known as TOCA1)
  • Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 (ARHGEF6 also known as COOL2)
  • CAP-GLY domain containing linker protein 1 (CLIP1)
  • activated CDC2 binds to E-cadherin in a GTP-dependent manner, and the binding of Cdc42 is essential for CDC42 to induce the dissolution of adherens junctions
  • interaction with RAC1 (CDC42 and RAC1 regulate actin reorganization during mitosis through a pathway that is distinct from the PI(3)K pathway and both pathways are required for the proper spindle orientation parallel to the substratum in adherent cells)
  • OBSCN is a specific activator of RHOQ but not the Rho GTPases RAC1 and CDC42
  • CDC42-GDP can inhibit RRAS2 activation by RASGRF1, RASGRF2
  • molecular link between UBE2I and the metastasis genes such as CDC42 and CXCR4, and thus provide new insight into the mechanism by which UBE2I9 promotes tumor invasion and metastasis
  • role of ARHGDIA as a CDC42 cycling factor
  • interacting with CDC42 (ARHGEF9 and CDC42 are major regulators of GABAergic postsynaptic densities)
  • activated by cholesterol depletion, interacts with NPC1L1 and facilitates its transport to the plasma membrane upon cholesterol depletion
  • phosphatidylserine--and presumably its polarization--are required for optimal Cdc42 targeting and activation during cell division and mating
  • OPHN1 exhibits strong GTPase-stimulating activity towards RHOA, CDC42, and RAC1 and regulates cell adhesion and spreading
  • PTK2 modulates CDC42 activity downstream of positive and negative axon guidance cues
  • DOCK8 is a CDC42 activator critical for interstitial dendritic cell migration during immune responses
  • may participate in localization of mRNAs encoding CCDC42 signaling factors in neurites, and thereby may regulate actin dynamics and control neuronal morphogenesis
  • nuclear movement during myotube formation is microtubule and dynein dependent and is regulated by CDC42, PARD6A and PARD3
  • SH3BP1, a GTPase-activating protein for CDC42 and RAC1, is a regulator of junction assembly and epithelial morphogenesis
  • promotes transendothelial migration of cancer cells through ITGB1
  • ARHGAP21 is a negative regulator of Rho-GTPases, particularly CDC42
  • interaction between CDC42 and intersectin (ITSN1), a specific CDC42 guanine nucleotide exchange factor
  • temporal interaction between CDC42 and the exocyst complex during large particle uptake
  • action of DOCK7 may involve the coordinated integration of CDC42/RAC1 signaling in the context of the membrane recruitment of a DOCK7 GEF complex
  • TGFBR3 and CDC42 colocalize to filopodial structures and co-complex in a ARRB2 dependent, and a TGFBR1/TGFBR2 independent manner
  • TGFBR3 is a novel regulator of BAIAP2/WAS via CDC42 to regulate filopodial formation and cell adhesion
  • CDC42 and EXOC5 cooperate in ciliogenesis
  • role for CDC42 in an FGF8A-specific signaling pathway essential for vertebrate neuronal development
  • ITSN1 is an important general regulator of CDC42-, NCK1- and WASL-dependent actin polymerisation
  • 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
  • YES1 is a proximal glucose-specific activator of cell division cycle control protein 42 (CDC42) in pancreatic islet beta cells
  • STARD13 is a RHO-GAP that specifically inhibits the function of RHOA and CDC42
  • concerted action of ARF1, ARHGAP21, and CDC42 to regulate fluid phase endocytosis
  • PICK1 binds RAC1 and CDC42, via distinct but overlapping binding sites
  • role of PTBP1 in tumorigenesis may be partly mediated by its regulation of CDC42 alternative splicing and CDC42-v2 might function as a tumor suppressor
  • MARCKS upregulation increases VSMC motility by activation of RAC1 and CDC42
  • ATP8B1 enables CDC42 clustering during enterocyte polarization
  • TNF regulates GRID2 gene expression by activating CDC42 and GOPC genes
  • ERFFI1 bind to and inhibit the Rho GTPase CDC42 to suppress cytoskeletal rearrangement
  • WASL positively regulates demarcation membrane system (DMS) development and proplatelet formation (PPF), and the Src family kinases in association with CDC42 regulate PPF through WASL
  • LRCH1 competes with CDC42 for interaction with DOCK8 and restrains T cell migration
  • during macrophage migration, DOCK8 links CDC42 activation to actomyosin dynamics through the association with LURAP1
  • ITSN1 and ITSN2 are podocytic guanine nucleotide exchange factors for CDC42
  • RASIP1 regulates likely CDC42 activity to regulate cell junctions and cytoskeleton organization, which are both activities required for lymphatic lumen maintenance
  • ODF2, a prevalent protein involved in the formation of spermatid-specific cytoskeletal structures, is a putative binding partnerof CDC42
  • CDC42-activated PAK2 mediates cytostasis, whereas caspase 3-cleaved PAK2 contributes to apoptosis
    • cell & other
    REGULATION
    activated by differentially expressed in FDCP 6 homolog (DEF6)
    the bacterial toxin SopE
    inhibited by inactivated by SLIT
    Other regulated by IQGAP1 (serves as a phosphorylation-sensitive conformation switch to regulate the coupling of cell growth and division through a novel CDC42-MTOR pathway, dysregulation of which generates cellular transformation)
    influence of membrane dynamics on the localization and activation of CDC42 and consequently on directed cell migration
    histaminylation of Gln residues is a novel posttranslational modification implicated in GNAQ
    RASIP1 regulates CDC42 activity
    ASSOCIATED DISORDERS
    corresponding disease(s) MTCMR
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancers
    Susceptibility to osteoporosis
    Variant & Polymorphism SNP increasing the risk of osteoporosis
    Candidate gene for holoprosencephaly
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    ZCL278 is a small molecule that specifically targets CDC42–ITSN1 interaction and inhibits CDC42-mediated cellular processes, thus providing a tool for research of CDC42 subclass of Rho GTPases in pathogenesis, such as cancer and neurological disorders
    miscelleaneousurinarychronic kidney disease
    maintaining necessary CDC42 would be one potent way to prevent proteinuria kidney diseases
    ANIMAL & CELL MODELS
  • mice with a keratinocyte-restricted deletion of the Cdc42 gene were born without obvious defects, but showed highly impaired hair coat development
  • conditionally deletion of Cdc42 gene in telencephalic neural progenitors from mouse embryos abolishes the apical localization of PAR6, aPKC, E-cadherin, beta-catenin, and Numb proteins in the neuroepithelium, and severely impairs the extension of nestin-positive radial fibers
  • brain and neuronal development are severely disrupted in Cdc42-deficient mice
  • mice with podocyte-specific deletion of Cdc42 had severe proteinuria, podocyte foot process effacement, and glomerulosclerosis beginning as early as 10 days of age
  • mice lacking Cdc42 specifically in kidney tubular epithelial cells died of renal failure within weeks of birth
  • deletion of Cdc42 in mice could lead to increased adipocyte differentiation and decreased bone formation