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FLASH GENE
Symbol CDC42 contributors: shn/ - updated : 19-06-2013
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) (PMID;
  • 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
  • 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
  • concerted action of ARF1, ARHGAP21, and CDC42 to regulate fluid phase endocytosis
  • 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