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FLASH GENE
Symbol CDC42 contributors: shn/ - updated : 19-06-2016
HGNC name cell division cycle 42 (GTP binding protein, 25kDa)
HGNC id 1736
Location 1p36.12      Physical location : 22.379.119 - 22.419.435
Synonym name
  • cell division cycle 42
  • GTP binding protein, 25kDa
  • growth-regulating protein
  • small GTP binding protein CDC42
  • dJ224A6.1.2 (cell division cycle 42 (GTP-binding protein, 25kD))
  • Synonym symbol(s) G25K, G25B, FLJ32734, CCDC42A, CDC42Hs
    EC.number 3.6.5.1/3.6.5.2/ 3.6.5.3/ 3.6.5.4
    DNA
    TYPE functioning gene
    STRUCTURE 40.32 kb     6 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - D1S2828 - D1S2725 - CDC42 - D1S2702 - D1S2864 - cen
    Physical map
    KIF17 1p36.13 kinesin family member 17 LOC388602 1 LOC388602 LOC388603 1 LOC388603 HP1-BP74 1p36.12 HP1-BP74 EIF4G3 11p15 eukaryotic translation initiation factor 4 gamma, 3 LOC388604 1 LOC388604 ECE1 1p36.1 endothelin converting enzyme 1 LOC391014 1 similar to protein phosphatase 1, regulatory (inhibitor) subunit 11 isoform 1; hemochromatosis candidate gene V; t-complex-associated-testis-expressed 5; inhibitor-3 LOC343381 1p36.12 similar to KIAA0454 protein LOC391015 1 similar to hypothetical protein AE2 LOC388605 1 similar to heparan-sulfate 6-sulfotransferase LOC391016 1 similar to KIAA0445 protein AE2 1p36.12 hypothetical protein AE2 ALPL 1p36.1 alkaline phosphatase, liver/bone/kidney RAP1GA1 1p36.1 RAP1, GTPase activating protein 1 USP31 1p36.12 ubiquitin specific protease 31 HSPG2 1p36.11-p35 heparan sulfate proteoglycan 2 (perlecan) LOC391017 1 hypothetical gene supported by X89401; NM_000982 ELA3B 1p36.12 elastase 3B, pancreatic ELA3A 1p36.12 elastase 3A, pancreatic (protease E) HSPC157 1p36.12 HSPC157 protein CDC42 1p36.1 cell division cycle 42 (GTP binding protein, 25kDa) WNT4 1p36.23-p35.1 wingless-type MMTV integration site family, member 4 LOC343384 1p36.12 similar to peptidyl-Pro cis trans isomerase KIAA0478 1pter-q31.3 similar to peptidyl-Pro cis trans isomerase EPHA8 1p36.12 EphA8 C1QA 1p36.3-p34.1 complement component 1, q subcomponent, alpha polypeptide C1QG 1p36.3-p34.1 complement component 1, q subcomponent, gamma polypeptide C1QB 1p36.11 complement component 1, q subcomponent, beta polypeptide EPHB2 1p36.1-p35 EphB2 LOC127309 1p36.11 similar to RIKEN cDNA 4930549C01 KIAA0601 1p36.11 KIAA0601 protein LUZP1 1p36 leucine zipper protein 1 LOC391018 1 similar to RIKEN cDNA 2410002F23 HTR1D 1p35 5-hydroxytryptamine (serotonin) receptor 1D LOC391019 1 similar to 60S ribosomal protein L29 (Cell surface heparin binding protein HIP) HNRPR 1p36.11 heterogeneous nuclear ribonucleoprotein R
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 2182 21.3 191 - 2009 19454477
  • missing exon 7
  • overlapping or tightly linked to BB1L2
  • 6 - 1530 23 191 placenta 2009 19454477
  • missing exon 6
  • overlapping or tightly linked to BB1L3
  • 7 - 2308 - 191 - 2009 19454477
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Cardiovascularheart   highly
    Nervousbrain   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    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
  • 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
  • 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
  • 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
  • PTK2 modulates CDC42 activity downstream of positive and negative axon guidance cues
  • nuclear movement during myotube formation is microtubule and dynein dependent and is regulated by CDC42, PARD6A and PARD3
  • 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
  • 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
  • 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
  • MARCKS upregulation increases VSMC motility by activation of RAC1 and CDC42
  • TNF regulates GRID2 gene expression by activating CDC42 and GOPC genes
  • 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
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancers
    Susceptibility
    Variant & Polymorphism
    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
    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