RBCC Red Blood Cell Collection

CDC42 [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Cell division control protein 42 homolog (G25K GTP-binding protein; Flags: Precursor)

hRBCD IPI00016786
IPI00016786 Splice isoform 2 of P60953 Cell division control protein 42 homolog Splice isoform 2 of P60953 Cell division control protein 42 homolog membrane n/a n/a 1 1 1 n/a n/a n/a 2 n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a membrane bound splice isoforms 1 and 2 expected molecular weight found in band > 188 kDa together with ubiquitin

UniProt P60953
ID CDC42_HUMAN Reviewed; 191 AA.
AC P60953; P21181; P25763; Q7L8R5; Q9UDI2;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 08-FEB-2011, sequence version 2.
DT 22-JAN-2014, entry version 137.
DE RecName: Full=Cell division control protein 42 homolog;
DE AltName: Full=G25K GTP-binding protein;
DE Flags: Precursor;
GN Name=CDC42;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=2122236;
RA Munemitsu S., Innis M.A., Clark R., McCormick F., Ullrich A.,
RA Polakis P.;
RT "Molecular cloning and expression of a G25K cDNA, the human homolog of
RT the yeast cell cycle gene CDC42.";
RL Mol. Cell. Biol. 10:5977-5982(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
RX PubMed=2124704; DOI=10.1073/pnas.87.24.9853;
RA Shinjo K., Koland J.G., Hart M.J., Narasimhan V., Johnson D.I.,
RA Evans T., Cerione R.A.;
RT "Molecular cloning of the gene for the human placental GTP-binding
RT protein Gp (G25K): identification of this GTP-binding protein as the
RT human homolog of the yeast cell-division-cycle protein CDC42.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9853-9857(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RA Rhodes S., Huckle E.;
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Placenta;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction
RT sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cervix, Placenta, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 67-83 (ISOFORM 2), PARTIAL PROTEIN SEQUENCE
RP (ISOFORM 1), AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 97-107; 134-144 AND 167-183 (ISOFORM 2).
RC TISSUE=Neutrophil;
RX PubMed=8504089; DOI=10.1021/bi00072a029;
RA Kwong C.H., Malech H.L., Rotrosen D., Leto T.L.;
RT "Regulation of the human neutrophil NADPH oxidase by rho-related G-
RT proteins.";
RL Biochemistry 32:5711-5717(1993).
RN [10]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=2496687; DOI=10.1016/0006-291X(89)91615-X;
RA Polakis P.G., Snyderman R., Evans T.;
RT "Characterization of G25K, a GTP-binding protein containing a novel
RT putative nucleotide binding domain.";
RL Biochem. Biophys. Res. Commun. 160:25-32(1989).
RN [11]
RP INTERACTION WITH CDC42EP1; CDC42EP2; CDC42EP3 AND CDC42EP5.
RC TISSUE=Embryo;
RX PubMed=10490598;
RA Joberty G., Perlungher R.R., Macara I.G.;
RT "The Borgs, a new family of Cdc42 and TC10 GTPase-interacting
RT proteins.";
RL Mol. Cell. Biol. 19:6585-6597(1999).
RN [12]
RP INTERACTION WITH CSPG4.
RX PubMed=10587647; DOI=10.1038/70302;
RA Eisenmann K.M., McCarthy J.B., Simpson M.A., Keely P.J., Guan J.-L.,
RA Tachibana K., Lim L., Manser E., Furcht L.T., Iida J.;
RT "Melanoma chondroitin sulphate proteoglycan regulates cell spreading
RT through Cdc42, Ack-1 and p130cas.";
RL Nat. Cell Biol. 1:507-513(1999).
RN [13]
RP INTERACTION WITH CDC42SE1 AND CDC42SE2.
RX PubMed=10816584; DOI=10.1074/jbc.M002832200;
RA Pirone D.M., Fukuhara S., Gutkind J.S., Burbelo P.D.;
RT "SPECs, small binding proteins for Cdc42.";
RL J. Biol. Chem. 275:22650-22656(2000).
RN [14]
RP INTERACTION WITH PARD6A, AND MUTAGENESIS OF GLY-12.
RX PubMed=10954424;
RA Johansson A.-S., Driessens M., Aspenstroem P.;
RT "The mammalian homologue of the Caenorhabditis elegans polarity
RT protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and
RT Rac1.";
RL J. Cell Sci. 113:3267-3275(2000).
RN [15]
RP INTERACTION WITH BAIAP2.
RX PubMed=11130076; DOI=10.1038/35047107;
RA Miki H., Yamaguchi H., Suetsugu S., Takenawa T.;
RT "IRSp53 is an essential intermediate between Rac and WAVE in the
RT regulation of membrane ruffling.";
RL Nature 408:732-735(2000).
RN [16]
RP INTERACTION WITH PARD6A; PARD6B AND PARD6G, SUBUNIT OF A COMPLEX
RP CONTAINING PRKCI AND PARD6B, AND MUTAGENESIS OF THR-17 AND GLN-61.
RX PubMed=11260256; DOI=10.1046/j.1365-2443.2001.00404.x;
RA Noda Y., Takeya R., Ohno S., Naito S., Ito T., Sumimoto H.;
RT "Human homologues of the Caenorhabditis elegans cell polarity protein
RT PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to
RT atypical protein kinase C.";
RL Genes Cells 6:107-119(2001).
RN [17]
RP INTERACTION WITH ITGB1BP1.
RX PubMed=11807099; DOI=10.1083/jcb.200108030;
RA Degani S., Balzac F., Brancaccio M., Guazzone S., Retta S.F.,
RA Silengo L., Eva A., Tarone G.;
RT "The integrin cytoplasmic domain-associated protein ICAP-1 binds and
RT regulates Rho family GTPases during cell spreading.";
RL J. Cell Biol. 156:377-387(2002).
RN [18]
RP INTERACTION WITH DOCK9, AND ACTIVATION BY DOCK9.
RX PubMed=12172552; DOI=10.1038/ncb835;
RA Meller N., Irani-Tehrani M., Kiosses W.B., Del Pozo M.A.,
RA Schwartz M.A.;
RT "Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho
RT proteins.";
RL Nat. Cell Biol. 4:639-647(2002).
RN [19]
RP PHOSPHORYLATION AT TYR-64 BY SRC.
RX PubMed=14506284; DOI=10.1074/jbc.M307021200;
RA Tu S., Wu W.J., Wang J., Cerione R.A.;
RT "Epidermal growth factor-dependent regulation of Cdc42 is mediated by
RT the Src tyrosine kinase.";
RL J. Biol. Chem. 278:49293-49300(2003).
RN [20]
RP INTERACTION WITH USP6.
RX PubMed=12612085; DOI=10.1128/MCB.23.6.2151-2161.2003;
RA Masuda-Robens J.M., Kutney S.N., Qi H., Chou M.M.;
RT "The TRE17 oncogene encodes a component of a novel effector pathway
RT for Rho GTPases Cdc42 and Rac1 and stimulates actin remodeling.";
RL Mol. Cell. Biol. 23:2151-2161(2003).
RN [21]
RP FUNCTION, AND MUTAGENESIS OF GLY-12 AND THR-17.
RX PubMed=14978216; DOI=10.1091/mbc.E03-07-0493;
RA Gauthier-Campbell C., Bredt D.S., Murphy T.H., El-Husseini A.;
RT "Regulation of dendritic branching and filopodia formation in
RT hippocampal neurons by specific acylated protein motifs.";
RL Mol. Biol. Cell 15:2205-2217(2004).
RN [22]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15642749; DOI=10.1083/jcb.200408085;
RA Oceguera-Yanez F., Kimura K., Yasuda S., Higashida C., Kitamura T.,
RA Hiraoka Y., Haraguchi T., Narumiya S.;
RT "Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in
RT mitosis.";
RL J. Cell Biol. 168:221-232(2005).
RN [23]
RP FUNCTION IN CELL MIGRATION, AND INTERACTION WITH BCAR1; TNK2 AND CRK.
RX PubMed=17038317; DOI=10.1074/jbc.M604342200;
RA Modzelewska K., Newman L.P., Desai R., Keely P.J.;
RT "Ack1 mediates Cdc42-dependent cell migration and signaling to
RT p130Cas.";
RL J. Biol. Chem. 281:37527-37535(2006).
RN [24]
RP MUTAGENESIS OF GLY-12 AND THR-17.
RX PubMed=19029984; DOI=10.1038/nm.1879;
RA Shibata S., Nagase M., Yoshida S., Kawarazaki W., Kurihara H.,
RA Tanaka H., Miyoshi J., Takai Y., Fujita T.;
RT "Modification of mineralocorticoid receptor function by Rac1 GTPase:
RT implication in proteinuric kidney disease.";
RL Nat. Med. 14:1370-1376(2008).
RN [25]
RP AMPYLATION AT TYR-32, AND MUTAGENESIS OF TYR-32.
RX PubMed=19362538; DOI=10.1016/j.molcel.2009.03.008;
RA Worby C.A., Mattoo S., Kruger R.P., Corbeil L.B., Koller A.,
RA Mendez J.C., Zekarias B., Lazar C., Dixon J.E.;
RT "The fic domain: regulation of cell signaling by adenylylation.";
RL Mol. Cell 34:93-103(2009).
RN [26]
RP AMPYLATION AT THR-35.
RX PubMed=19039103; DOI=10.1126/science.1166382;
RA Yarbrough M.L., Li Y., Kinch L.N., Grishin N.V., Ball H.L., Orth K.;
RT "AMPylation of Rho GTPases by Vibrio VopS disrupts effector binding
RT and downstream signaling.";
RL Science 323:269-272(2009).
RN [27]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH NEK6.
RX PubMed=20873783; DOI=10.1021/pr100562w;
RA Vaz Meirelles G., Ferreira Lanza D.C., da Silva J.C.,
RA Santana Bernachi J., Paes Leme A.F., Kobarg J.;
RT "Characterization of hNek6 interactome reveals an important role for
RT its short N-terminal domain and colocalization with proteins at the
RT centrosome.";
RL J. Proteome Res. 9:6298-6316(2010).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [29]
RP INTERACTION WITH ARHGEF16.
RX PubMed=21139582; DOI=10.1038/sj.bjc.6606026;
RA Oliver A.W., He X., Borthwick K., Donne A.J., Hampson L.,
RA Hampson I.N.;
RT "The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, which
RT activates Cdc42.";
RL Br. J. Cancer 104:324-331(2011).
RN [30]
RP INTERACTION WITH ARHGDIA.
RX PubMed=23434736; DOI=10.1136/jmedgenet-2012-101442;
RA Gupta I.R., Baldwin C., Auguste D., Ha K.C., El Andalousi J.,
RA Fahiminiya S., Bitzan M., Bernard C., Akbari M.R., Narod S.A.,
RA Rosenblatt D.S., Majewski J., Takano T.;
RT "ARHGDIA: a novel gene implicated in nephrotic syndrome.";
RL J. Med. Genet. 50:330-338(2013).
RN [31]
RP STRUCTURE BY NMR.
RX PubMed=9220962; DOI=10.1021/bi970694x;
RA Feltham J.L., Dotsch V., Raza S., Manor D., Cerione R.A.,
RA Sutcliffe M.J., Wagner G., Oswald R.E.;
RT "Definition of the switch surface in the solution structure of
RT Cdc42Hs.";
RL Biochemistry 36:8755-8766(1997).
RN [32]
RP STRUCTURE BY NMR.
RX PubMed=9760238; DOI=10.1021/bi981352+;
RA Guo W., Sutcliffe M.J., Cerione R.A., Oswald R.E.;
RT "Identification of the binding surface on Cdc42Hs for p21-activated
RT kinase.";
RL Biochemistry 37:14030-14037(1998).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF COMPLEX WITH RHOGAP.
RX PubMed=9262406; DOI=10.1038/41805;
RA Rittinger K., Walker P.A., Eccleston J.F., Nurmahomed K., Owen D.,
RA Laue E., Gamblin S.J., Smerdon S.J.;
RT "Crystal structure of a small G protein in complex with the GTPase-
RT activating protein rhoGAP.";
RL Nature 388:693-697(1997).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF VAL-12 MUTANT.
RX PubMed=10211824;
RA Rudolph M.G., Wittinghofer A., Vetter I.R.;
RT "Nucleotide binding to the G12V-mutant of Cdc42 investigated by X-ray
RT diffraction and fluorescence spectroscopy: two different nucleotide
RT states in one crystal.";
RL Protein Sci. 8:778-787(1999).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RA Kongsaeree P., Cerione R.A., Clardy J.C.;
RT "The structure determination of CDC42Hs and GDP complex.";
RL Submitted (JUN-1997) to the PDB data bank.
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-188 IN COMPLEX WITH DOCK9.
RX PubMed=19745154; DOI=10.1126/science.1174468;
RA Yang J., Zhang Z., Roe S.M., Marshall C.J., Barford D.;
RT "Activation of Rho GTPases by DOCK exchange factors is mediated by a
RT nucleotide sensor.";
RL Science 325:1398-1402(2009).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-181 IN COMPLEX WITH
RP H.SOMNUS IBPA AND GDP, AND AMPYLATION AT TYR-32.
RX PubMed=20622875; DOI=10.1038/nsmb.1867;
RA Xiao J., Worby C.A., Mattoo S., Sankaran B., Dixon J.E.;
RT "Structural basis of Fic-mediated adenylylation.";
RL Nat. Struct. Mol. Biol. 17:1004-1010(2010).
CC -!- FUNCTION: Plasma membrane-associated small GTPase which cycles
CC between an active GTP-bound and an inactive GDP-bound state. In
CC active state binds to a variety of effector proteins to regulate
CC cellular responses. Involved in epithelial cell polarization
CC processes. Regulates the bipolar attachment of spindle
CC microtubules to kinetochores before chromosome congression in
CC metaphase. Plays a role in the extension and maintenance of the
CC formation of thin, actin-rich surface projections called
CC filopodia. Mediates CDC42-dependent cell migration.
CC -!- ENZYME REGULATION: Regulated by guanine nucleotide exchange
CC factors (GEFs) which promote the exchange of bound GDP for free
CC GTP, GTPase activating proteins (GAPs) which increase the GTP
CC hydrolysis activity, and GDP dissociation inhibitors which inhibit
CC the dissociation of the nucleotide from the GTPase.
CC -!- SUBUNIT: The GTP-bound form interacts with CCPG1 (By similarity).
CC Interacts with CDC42EP1, CDC42EP2, CDC42EP3, CDC42EP4, CDC42EP5,
CC CDC42SE1, CDC42SE2, PARD6A, PARD6B and PARD6G (in a GTP-dependent
CC manner). Interacts with activated CSPG4 and with BAIAP2. Interacts
CC with Zizimin1/DOCK9 and Zizimin2/DOCK11, which activate it by
CC exchanging GDP for GTP. Interacts with NET1 and ARHGAP33/TCGAP.
CC Part of a complex with PARD3, PARD6A or PARD6B and PRKCI or PRKCZ.
CC Interacts with USP6. May interact with ARHGEF16; responsible for
CC the activation of CDC42 by the viral protein HPV16 E6. Interacts
CC with NEK6. Part of a collagen stimulated complex involved in cell
CC migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas.
CC Interacts with ITGB1BP1. Interacts with ARHGDIA; this interaction
CC inactivates and stabilizes CDC42.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-81752, EBI-81752;
CC Q07960:ARHGAP1; NbExp=2; IntAct=EBI-287394, EBI-602762;
CC Q9UQB8:BAIAP2; NbExp=2; IntAct=EBI-287394, EBI-525456;
CC Q9VEX9:Bin1 (xeno); NbExp=2; IntAct=EBI-81752, EBI-129424;
CC Q5VT25:CDC42BPA; NbExp=5; IntAct=EBI-81752, EBI-689171;
CC Q00587:CDC42EP1; NbExp=3; IntAct=EBI-81752, EBI-744130;
CC P46940:IQGAP1; NbExp=2; IntAct=EBI-81752, EBI-297509;
CC Q15811:ITSN1; NbExp=2; IntAct=EBI-3625591, EBI-602041;
CC Q5S007:LRRK2; NbExp=3; IntAct=EBI-81752, EBI-5323863;
CC Q16584:MAP3K11; NbExp=2; IntAct=EBI-81752, EBI-49961;
CC Q96L34:MARK4; NbExp=2; IntAct=EBI-81752, EBI-302319;
CC Q64096:Mcf2l (xeno); NbExp=3; IntAct=EBI-287394, EBI-602123;
CC Q13153:PAK1; NbExp=7; IntAct=EBI-81752, EBI-1307;
CC O75914:PAK3; NbExp=2; IntAct=EBI-287394, EBI-3389553;
CC Q61036:Pak3 (xeno); NbExp=3; IntAct=EBI-81752, EBI-457317;
CC O96013:PAK4; NbExp=2; IntAct=EBI-81752, EBI-713738;
CC Q9NPB6:PARD6A; NbExp=7; IntAct=EBI-81752, EBI-81876;
CC Q9BYG5:PARD6B; NbExp=7; IntAct=EBI-81752, EBI-295391;
CC Q9JK83:Pard6b (xeno); NbExp=6; IntAct=EBI-81752, EBI-81861;
CC Q9BYG4:PARD6G; NbExp=5; IntAct=EBI-81752, EBI-295417;
CC P41743:PRKCI; NbExp=5; IntAct=EBI-81752, EBI-286199;
CC O52623:sopE (xeno); NbExp=2; IntAct=EBI-81752, EBI-602254;
CC Q07912:TNK2; NbExp=2; IntAct=EBI-287394, EBI-603457;
CC P42768:WAS; NbExp=10; IntAct=EBI-81752, EBI-346375;
CC O00401:WASL; NbExp=3; IntAct=EBI-81752, EBI-957615;
CC O08816:Wasl (xeno); NbExp=2; IntAct=EBI-81752, EBI-6142604;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic
CC side (Potential). Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome. Cytoplasm, cytoskeleton, spindle. Midbody.
CC Note=Localizes to spindle during prometaphase cells. Moves to the
CC central spindle as cells progressed through anaphase to telophase.
CC Localizes at the end of cytokinesis in the intercellular bridge
CC formed between two daughter cells. Its localization is regulated
CC by the activities of guanine nucleotide exchange factor ECT2 and
CC GTPase activating protein RACGAP1. Colocalizes with NEK6 in the
CC centrosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2; Synonyms=Placental;
CC IsoId=P60953-2, P21181-4;
CC Sequence=Displayed;
CC Name=1; Synonyms=Brain;
CC IsoId=P60953-1, P21181-1;
CC Sequence=VSP_040583, VSP_040584;
CC -!- PTM: AMPylation at Tyr-32 and Thr-35 are mediated by bacterial
CC enzymes in case of infection by H.somnus and V.parahaemolyticus,
CC respectively. AMPylation occurs in the effector region and leads
CC to inactivation of the GTPase activity by preventing the
CC interaction with downstream effectors, thereby inhibiting actin
CC assembly in infected cells. It is unclear whether some human
CC enzyme mediates AMPylation; FICD has such ability in vitro but
CC additional experiments remain to be done to confirm results in
CC vivo.
CC -!- PTM: Phosphorylated by SRC in an EGF-dependent manner, this
CC stimulates the binding of the Rho-GDP dissociation inhibitor
CC RhoGDI.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family.
CC CDC42 subfamily.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CDC42ID40012ch1p36.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdc42/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M35543; AAA52494.1; -; mRNA.
DR EMBL; M57298; AAA52592.1; -; mRNA.
DR EMBL; AL121734; CAB57325.1; -; mRNA.
DR EMBL; AL121735; CAB57326.1; -; mRNA.
DR EMBL; AF498962; AAM21109.1; -; mRNA.
DR EMBL; AF498963; AAM21110.1; -; mRNA.
DR EMBL; AY673602; AAT70721.1; -; Genomic_DNA.
DR EMBL; AL031281; CAB52602.1; -; Genomic_DNA.
DR EMBL; AL031281; CAD92551.1; -; Genomic_DNA.
DR EMBL; BC002711; AAH02711.1; -; mRNA.
DR EMBL; BC003682; AAH03682.1; -; mRNA.
DR EMBL; BC018266; AAH18266.1; -; mRNA.
DR PIR; A36382; A36382.
DR PIR; A39265; A39265.
DR RefSeq; NP_001034891.1; NM_001039802.1.
DR RefSeq; NP_001782.1; NM_001791.3.
DR RefSeq; NP_426359.1; NM_044472.2.
DR RefSeq; XP_005246103.1; XM_005246046.1.
DR UniGene; Hs.467637; -.
DR PDB; 1A4R; X-ray; 2.50 A; A/B=1-191.
DR PDB; 1AJE; NMR; -; A=1-187.
DR PDB; 1AM4; X-ray; 2.70 A; D/E/F=2-177.
DR PDB; 1AN0; X-ray; 2.80 A; A/B=2-190.
DR PDB; 1CEE; NMR; -; A=1-179.
DR PDB; 1CF4; NMR; -; A=1-184.
DR PDB; 1DOA; X-ray; 2.60 A; A=1-188.
DR PDB; 1E0A; NMR; -; A=1-184.
DR PDB; 1EES; NMR; -; A=1-178.
DR PDB; 1GRN; X-ray; 2.10 A; A=1-191.
DR PDB; 1GZS; X-ray; 2.30 A; A/C=1-178.
DR PDB; 1KI1; X-ray; 2.30 A; A/C=1-187.
DR PDB; 1KZ7; X-ray; 2.40 A; B/D=1-187.
DR PDB; 1KZG; X-ray; 2.60 A; B/D=1-187.
DR PDB; 1NF3; X-ray; 2.10 A; A/B=2-191.
DR PDB; 2ASE; NMR; -; A=1-178.
DR PDB; 2DFK; X-ray; 2.15 A; B/D=1-191.
DR PDB; 2KB0; NMR; -; A=1-178.
DR PDB; 2NGR; X-ray; 1.90 A; A=1-191.
DR PDB; 2ODB; X-ray; 2.40 A; A=1-191.
DR PDB; 2QRZ; X-ray; 2.40 A; A/B=1-189.
DR PDB; 2WM9; X-ray; 2.20 A; B=1-188.
DR PDB; 2WMN; X-ray; 2.39 A; B=1-188.
DR PDB; 2WMO; X-ray; 2.20 A; B=1-188.
DR PDB; 3GCG; X-ray; 2.30 A; A=2-178.
DR PDB; 3QBV; X-ray; 2.65 A; A/C=1-178.
DR PDB; 3VHL; X-ray; 2.08 A; B=1-187.
DR PDB; 4DID; X-ray; 2.35 A; A=1-183.
DR PDB; 4ITR; X-ray; 2.30 A; C/D=1-191.
DR PDBsum; 1A4R; -.
DR PDBsum; 1AJE; -.
DR PDBsum; 1AM4; -.
DR PDBsum; 1AN0; -.
DR PDBsum; 1CEE; -.
DR PDBsum; 1CF4; -.
DR PDBsum; 1DOA; -.
DR PDBsum; 1E0A; -.
DR PDBsum; 1EES; -.
DR PDBsum; 1GRN; -.
DR PDBsum; 1GZS; -.
DR PDBsum; 1KI1; -.
DR PDBsum; 1KZ7; -.
DR PDBsum; 1KZG; -.
DR PDBsum; 1NF3; -.
DR PDBsum; 2ASE; -.
DR PDBsum; 2DFK; -.
DR PDBsum; 2KB0; -.
DR PDBsum; 2NGR; -.
DR PDBsum; 2ODB; -.
DR PDBsum; 2QRZ; -.
DR PDBsum; 2WM9; -.
DR PDBsum; 2WMN; -.
DR PDBsum; 2WMO; -.
DR PDBsum; 3GCG; -.
DR PDBsum; 3QBV; -.
DR PDBsum; 3VHL; -.
DR PDBsum; 4DID; -.
DR PDBsum; 4ITR; -.
DR ProteinModelPortal; P60953; -.
DR SMR; P60953; 1-191.
DR DIP; DIP-31097N; -.
DR IntAct; P60953; 113.
DR MINT; MINT-94609; -.
DR STRING; 9606.ENSP00000314458; -.
DR BindingDB; P60953; -.
DR ChEMBL; CHEMBL6088; -.
DR PhosphoSite; P60953; -.
DR DMDM; 46397381; -.
DR PaxDb; P60953; -.
DR PRIDE; P60953; -.
DR DNASU; 998; -.
DR Ensembl; ENST00000315554; ENSP00000314458; ENSG00000070831.
DR Ensembl; ENST00000344548; ENSP00000341072; ENSG00000070831.
DR Ensembl; ENST00000400259; ENSP00000383118; ENSG00000070831.
DR GeneID; 998; -.
DR KEGG; hsa:998; -.
DR UCSC; uc001bfq.3; human.
DR CTD; 998; -.
DR GeneCards; GC01P022379; -.
DR HGNC; HGNC:1736; CDC42.
DR HPA; CAB004360; -.
DR MIM; 116952; gene.
DR neXtProt; NX_P60953; -.
DR PharmGKB; PA26266; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000233974; -.
DR HOVERGEN; HBG009351; -.
DR KO; K04393; -.
DR OMA; ITMEQGE; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR Reactome; REACT_96538; Developmental Biology.
DR SignaLink; P60953; -.
DR ChiTaRS; CDC42; human.
DR EvolutionaryTrace; P60953; -.
DR GeneWiki; CDC42; -.
DR GenomeRNAi; 998; -.
DR NextBio; 4192; -.
DR PMAP-CutDB; P60953; -.
DR PRO; PR:P60953; -.
DR ArrayExpress; P60953; -.
DR Bgee; P60953; -.
DR CleanEx; HS_CDC42; -.
DR Genevestigator; P60953; -.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:BHF-UCL.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:BHF-UCL.
DR GO; GO:0043025; C:neuronal cell body; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030141; C:secretory granule; IEA:Ensembl.
DR GO; GO:0051233; C:spindle midzone; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; TAS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IDA:BHF-UCL.
DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0090135; P:actin filament branching; IEA:Ensembl.
DR GO; GO:0051017; P:actin filament bundle assembly; IEA:Ensembl.
DR GO; GO:0034332; P:adherens junction organization; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0060070; P:canonical Wnt receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0003161; P:cardiac conduction system development; IEA:Ensembl.
DR GO; GO:0034613; P:cellular protein localization; IEA:Ensembl.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0090136; P:epithelial cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0060684; P:epithelial-mesenchymal cell signaling; IEA:Ensembl.
DR GO; GO:0051683; P:establishment of Golgi localization; ISS:BHF-UCL.
DR GO; GO:0035088; P:establishment or maintenance of apical/basal cell polarity; IEA:Ensembl.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; TAS:UniProtKB.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0046847; P:filopodium assembly; IEA:Ensembl.
DR GO; GO:0007030; P:Golgi organization; ISS:BHF-UCL.
DR GO; GO:0031069; P:hair follicle morphogenesis; IEA:Ensembl.
DR GO; GO:0060789; P:hair follicle placode formation; IEA:Ensembl.
DR GO; GO:0060047; P:heart contraction; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0031424; P:keratinization; IEA:Ensembl.
DR GO; GO:0003334; P:keratinocyte development; IEA:Ensembl.
DR GO; GO:0030225; P:macrophage differentiation; TAS:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0042692; P:muscle cell differentiation; TAS:Reactome.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0031333; P:negative regulation of protein complex assembly; IPI:UniProtKB.
DR GO; GO:0048664; P:neuron fate determination; IEA:Ensembl.
DR GO; GO:0007097; P:nuclear migration; IEA:Ensembl.
DR GO; GO:0072384; P:organelle transport along microtubule; ISS:BHF-UCL.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB.
DR GO; GO:0045740; P:positive regulation of DNA replication; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0071338; P:positive regulation of hair follicle cell proliferation; IEA:Ensembl.
DR GO; GO:0090316; P:positive regulation of intracellular protein transport; IEA:Ensembl.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl.
DR GO; GO:0048554; P:positive regulation of metalloenzyme activity; IEA:Ensembl.
DR GO; GO:0051149; P:positive regulation of muscle cell differentiation; TAS:Reactome.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IEA:Ensembl.
DR GO; GO:0031274; P:positive regulation of pseudopodium assembly; IDA:UniProtKB.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IDA:UniProtKB.
DR GO; GO:0051835; P:positive regulation of synapse structural plasticity; IEA:Ensembl.
DR GO; GO:0051988; P:regulation of attachment of spindle microtubules to kinetochore; IMP:UniProtKB.
DR GO; GO:0051489; P:regulation of filopodium assembly; IDA:UniProtKB.
DR GO; GO:0007088; P:regulation of mitosis; IEA:Ensembl.
DR GO; GO:0042176; P:regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0043497; P:regulation of protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0045859; P:regulation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0031647; P:regulation of protein stability; IEA:Ensembl.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0002040; P:sprouting angiogenesis; IEA:Ensembl.
DR GO; GO:0060661; P:submandibular salivary gland formation; IEA:Ensembl.
DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR003578; Small_GTPase_Rho.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00449; RASTRNSFRMNG.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51420; RHO; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Complete proteome;
KW Cytoplasm; Cytoskeleton; Differentiation; Direct protein sequencing;
KW GTP-binding; Lipoprotein; Membrane; Methylation; Neurogenesis;
KW Nucleotide-binding; Phosphoprotein; Prenylation; Reference proteome.
FT CHAIN 1 188 Cell division control protein 42 homolog.
FT /FTId=PRO_0000030425.
FT PROPEP 189 191 Removed in mature form.
FT /FTId=PRO_0000030426.
FT NP_BIND 10 17 GTP.
FT NP_BIND 57 61 GTP (By similarity).
FT NP_BIND 115 118 GTP.
FT MOTIF 32 40 Effector region (Potential).
FT MOD_RES 32 32 O-AMP-tyrosine; by Haemophilus IbpA.
FT MOD_RES 35 35 O-AMP-threonine; by Vibrio VopS.
FT MOD_RES 64 64 Phosphotyrosine; by SRC.
FT MOD_RES 188 188 Cysteine methyl ester (By similarity).
FT LIPID 188 188 S-geranylgeranyl cysteine (By
FT similarity).
FT VAR_SEQ 163 163 K -> R (in isoform 1).
FT /FTId=VSP_040583.
FT VAR_SEQ 182 191 PKKSRRCVLL -> TQPKRKCCIF (in isoform 1).
FT /FTId=VSP_040584.
FT MUTAGEN 12 12 G->V: Constitutively active. Interacts
FT with PARD6 proteins. Does not inhibit
FT filopodia formation. No effect on NR3C2
FT transcriptional activity.
FT MUTAGEN 17 17 T->N: Constitutively inactive. Does not
FT interact with PARD6 proteins. Inhibits
FT filopodia formation. No effect on NR3C2
FT transcriptional activity.
FT MUTAGEN 32 32 Y->F: Abolishes AMPylation by Haemophilus
FT IbpA.
FT MUTAGEN 61 61 Q->L: Constitutively active. Interacts
FT with PARD6 proteins.
FT STRAND 2 11
FT TURN 12 14
FT HELIX 16 25
FT HELIX 29 31
FT STRAND 36 46
FT STRAND 49 58
FT HELIX 62 64
FT TURN 65 67
FT HELIX 68 71
FT STRAND 72 74
FT STRAND 76 83
FT HELIX 87 95
FT HELIX 97 104
FT STRAND 105 107
FT STRAND 110 115
FT HELIX 117 121
FT HELIX 123 130
FT TURN 131 133
FT HELIX 139 148
FT STRAND 154 156
FT TURN 159 161
FT TURN 162 164
FT HELIX 165 176
FT STRAND 179 181
FT TURN 184 186
SQ SEQUENCE 191 AA; 21259 MW; 51A437E22A4D8FFF CRC64;
MQTIKCVVVG DGAVGKTCLL ISYTTNKFPS EYVPTVFDNY AVTVMIGGEP YTLGLFDTAG
QEDYDRLRPL SYPQTDVFLV CFSVVSPSSF ENVKEKWVPE ITHHCPKTPF LLVGTQIDLR
DDPSTIEKLA KNKQKPITPE TAEKLARDLK AVKYVECSAL TQKGLKNVFD EAILAALEPP
EPKKSRRCVL L
//

MIM 116952
*RECORD*
*FIELD* NO
116952
*FIELD* TI
*116952 CELL DIVISION CYCLE 42; CDC42
;;GTP-BINDING PROTEIN, 25-KD; G25K
*FIELD* TX
read more
DESCRIPTION

CDC42 is a Ras (see 190020)-related GTP-binding protein. It is
implicated in a variety of biologic activities, including establishment
of cell polarity in yeast, regulation of cell morphology, motility, and
cell cycle progression in mammalian cells, and induction of malignant
transformation (summary by Wu et al., 2000).

CLONING

Shinjo et al. (1990) isolated cDNA clones that code for cdc42, a low
molecular weight GTP-binding protein originally designated G(p) and also
called G25K, from a human placenta library. The predicted amino acid
sequence of the protein was very similar to those of various members of
the RAS superfamily of low molecular weight GTP-binding proteins,
including NRAS, KRAS, HRAS, and the RHO proteins. The highest degree of
sequence identity (80%) was found with the Saccharomyces cerevisiae cell
division cycle protein CDC42. The human placental gene complemented a
cdc42 mutation in S. cerevisiae. Munemitsu et al. (1990) presented
further evidence that G25K is the human homolog of the CDC42 gene
product.

Marks and Kwiatkowski (1996) identified 2 isoforms of mouse Cdc42. They
demonstrated that the 2 murine isoforms arise from a single gene by
alternative splicing. Although one is expressed in a wide variety of
tissues, the second isoform appeared to be expressed exclusively in
brain.

GENE FUNCTION

Erickson et al. (1996) used cell fractionation and immunofluorescence to
show that cdc42 is localized to the Golgi apparatus of mammalian cells.
It colocalizes with the nonclathrin coat proteins ARF3 (103190) and COPB
(600959) and its Golgi localization is disrupted by the drug brefeldin
A. Based on their findings, Erickson et al. (1996) suggested that cdc42
may be involved in the delivery of newly synthesized proteins and lipids
to the plasma membrane and that the GTP-binding/GTPase cycle may dictate
its subcellular localization.

By screening rat brain cytosol for proteins that interacted with
Ras-related GTPases, or p21 proteins, of the Rho (RHOA; 165390)
subfamily, Manser et al. (1994) identified 3 proteins, designated PAKs
(see PAK1; 602590) that interacted with the GTP-bound forms of human
CDC42 and RAC1 (602048), but not RHOA. Brown et al. (1996) found that
activity of human PAK1 was induced by coexpression with RAC1 or CDC42.

Zheng et al. (1996) reported that the FGD1 protein (305400) acts as a
cdc42-specific GDP-GTP exchange factor. Cells expressing a fragment of
the FGD1 protein encompassing the pleckstrin and Dbl homology domains
activated 2 elements downstream of cdc42, namely, Jun kinase (165160)
and p70 S6 kinase.

Manser et al. (1993) identified ACK1 (606994) as a binding partner and
inhibitor of the GTP-bound form of CDC42. Interaction between GTP-CDC42
and ACK1 inhibited both the intrinsic and GAP-stimulated GTPase activity
of CDC42.

CDC42 can regulate the actin cytoskeleton through activation of WASP
family members (see 301000). Activation relieves an autoinhibitory
contact between the GTPase-binding domain and the C-terminal region of
WASP proteins. Kim et al. (2000) reported the autoinhibited structure of
the GTPase-binding domain of WASP, which can be induced by the
C-terminal region or by organic cosolvents. In the autoinhibited
complex, intramolecular interactions with the GTPase-binding domain
occlude residues of the C terminus that regulate the Arp2/3
actin-nucleating complex (see 604221). Binding of CDC42 to the
GTPase-binding domain causes a dramatic conformational change, resulting
in disruption of the hydrophobic core and release of the C terminus,
enabling its interaction with the actin regulatory machinery.

Wu et al. (2000) identified a CDC42 mutant, Cdc42F28L, that binds GTP in
the absence of a guanine nucleotide exchange factor, but still
hydrolyzes GTP with a turnover number identical to that for wildtype
CDC42. Expression of this mutant in fibroblasts causes cellular
transformation, mimicking many of the characteristics of cells
transformed by the DBL oncoprotein (311030), a known guanine nucleotide
exchange factor for CDC42. Wu et al. (2000) searched for new CDC42
targets in an effort to understand how CDC42 mediates cellular
transformation. They identified the gamma-subunit of the coatomer
complex (gamma-COP; 604355) as a specific binding partner for activated
CDC42. The binding of CDC42 to gamma-COP is essential for a transforming
signal distinct from those elicited by Ras.

Dendritic cells (DCs) developmentally regulate antigen uptake by
controlling their endocytic capacity. Immature DCs actively internalize
antigen. Mature DCs, however, are poorly endocytic, functioning instead
to present antigens to T cells. Garrett et al. (2000) found that
endocytic downregulation reflects a decrease in endocytic activity
controlled by RHO family GTPases, especially CDC42. Blocking CDC42
function by toxin B treatment or injection of dominant-negative
inhibitors of CDC42 abrogated endocytosis in immature DCs. In mature
DCs, injection of constitutively active CDC42 or microbial delivery of a
CDC42 nucleotide exchange factor reactivated endocytosis. DCs regulated
endogenous levels of CDC42-GTP with activated CDC42 detectable only in
immature cells. Garrett et al. (2000) concluded that DCs developmentally
regulate endocytosis at least in part by controlling levels of activated
CDC42.

Using Mardin Darby canine kidney (MDCK) cells expressing Cdc42 mutants
defective in nucleotide binding or hydrolysis, Musch et al. (2001)
showed that Cdc42 differentially regulated the exit of apical and
basolateral proteins from the trans-Golgi network (TGN).
GTPase-deficient Cdc42 accelerated the exit of an apical marker from the
TGN and inhibited the release of basolateral proteins. Basolateral
protein transport by Cdc42 with an activating mutation was accompanied
by changes in the organization of the actin cytoskeleton.

Sin et al. (2002) used in vivo time-lapse imaging of optic tectal cells
in Xenopus laevis tadpoles to demonstrate that enhanced visual activity
driven by a light stimulus promotes dendritic arbor growth. The
stimulus-induced dendritic arbor growth requires glutamate receptor (see
138249)-mediated synaptic transmission, decreased RhoA (165390)
activity, and increased RAC and CDC42 activity. Sin et al. (2002)
concluded that their results delineated a role for Rho GTPases in the
structural plasticity driven by visual stimulation in vivo.

Morphologic changes in dendritic spines are believed to be caused by
dynamic regulation of actin polymerization. Irie and Yamaguchi (2002)
found that the EphB2 receptor tyrosine kinase (600997) physically
associates with the guanine nucleotide exchange factor intersectin-1
(602442) in cooperation with the actin-regulating protein N-WASP
(605056), which in turn activates Cdc42 and spine morphogenesis.

In higher eukaryotes, the small GTPase CDC42, acting through a
PAR6-atypical protein kinase C (see PKC-zeta, 176982) complex, is
required to establish cellular asymmetry during epithelial
morphogenesis, asymmetric cell division, and directed cell migration.
Etienne-Manneville and Hall (2003) used primary rat astrocytes in a cell
migration assay to demonstrate that PAR6-PKC-zeta interacts directly
with and regulates glycogen synthase kinase-3-beta (GSK3-beta; 605004)
to promote polarization of the centrosome and to control the direction
of cell protrusion. CDC42-dependent phosphorylation of GSK3-beta occurs
specifically at the leading edge of migrating cells, and induces the
interaction of APC (611731) protein with the plus ends of microtubules.
The association of APC with microtubules is essential for cell
polarization. Etienne-Manneville and Hall (2003) concluded that CDC42
regulates cell polarity through the spatial regulation of GSK3-beta and
APC.

Wu et al. (2003) presented evidence that activation of CDC42 protects
EGF receptor (EGFR; 131550) from the negative regulatory activity of CBL
(165360), a ubiquitin ligase.

Yasuda et al. (2004) demonstrated that Cdc42 and mDia3 (DIAPH2; 300108)
regulate microtubule attachment to kinetochores.

Nalbant et al. (2004) reported the development of a biosensor capable of
visualizing the changing activation of endogenous unlabeled Cdc42 in
living cells. With the use of a dye that reports protein interactions,
the biosensor revealed localized activation in the trans-Golgi
apparatus, microtubule-dependent Cdc42 activation at the cell periphery,
and activation kinetics precisely coordinated with cell extension and
retraction.

By electroporating genes into chicken presomitic mesenchymal cells,
Nakaya et al. (2004) demonstrated that Cdc42 and Rac1 play different
roles in mesenchymal-epithelial transition. Different levels of Cdc42
appeared to affect the binary decision between epithelial and
mesenchymal states. Proper levels of Rac1 were also necessary for
somitic epithelialization, since cells with either activated or
inhibited Rac1 failed to undergo correct epithelialization.

Using functional and proteomic screens to identify regulators of Cdc42,
Wells et al. (2006) identified a network of proteins that centered on
Rich1 (ARHGAP17; 608293) and organized apical polarity in canine kidney
epithelial cells. Rich1 bound the coiled-coil domain of Amot (300410)
and was thereby targeted to a complex at tight junctions containing the
PDZ domain-containing proteins Pals1 (MPP5; 606958), Patj (INADL;
603199), and Par3 (PARD3; 606745). Regulation of Cdc42 by Rich1 was
required for maintenance of tight junctions. The coiled-coil domain of
Amot was required for its localization to apical membranes and for Amot
to relocalize Pals1 and Par3 to internal puncta. Wells et al. (2006)
proposed that RICH1 and AMOT maintain tight junction integrity by
coordinated regulation of CDC42 and by linking specific components of
the tight junction to intracellular protein trafficking.

Formation of the apical surface and lumen is a fundamental step in
epithelial organ development. Martin-Belmonte et al. (2007) showed that
Pten (601728) localized to the apical plasma membrane during epithelial
morphogenesis to mediate enrichment of phosphatidylinositol
4,5-bisphosphate (PtdIns(4,5)P2) at this domain during cyst development
in a 3-dimensional Madin-Darby canine kidney cell system. Ectopic
PtdIns(4,5)P2 at the basolateral surface caused apical proteins to
relocalize to the basolateral surface. Annexin-2 (ANX2; 151740) bound
PtdIns(4,5)P2 and was recruited to the apical surface. Anx2 bound Cdc42
and recruited it to the apical surface, and Cdc42 in turn recruited the
Par6 (607484)/atypical protein kinase C (aPKC; see 176982) complex to
the apical surface. Loss of function of Pten, Anx2, Cdc42, or aPKC
prevented normal development of the apical surface and lumen.
Martin-Belmonte et al. (2007) concluded that PTEN, PtdIns(4,5)P2, ANX2,
CDC42, and aPKC control apical plasma membrane and lumen formation.

Hamann et al. (2007) found that both ASEF1 and ASEF2 were guanine
nucleotide exchange factors (GEFs) for CDC42, but not for RAC1 or RHOA.
ASEF2 required the lipid-modified form of CDC42. Using deletion mutants,
Hamann et al. (2007) showed that the tandem N-terminal ABR and SH3
domain (ABRSH3) of the ASEF proteins was required to bind the armadillo
repeat region of APC. ABRSH3 also functioned in an autoinhibitory
reaction by binding the C-terminal tails of ASEF1 and ASEF2 and
inhibiting their GEF activities. Deletion of ABRSH3 or coexpression of
the APC armadillo repeat sequence with full-length ASEF2 stimulated
filopodia formation in transfected HeLa cells. Hamann et al. (2007)
concluded that activation of ASEF1 and ASEF2 involves binding of APC to
ABRSH3, which disrupts the autoinhibitory interaction of ABRSH3 with the
ASEF C-terminal tail and allows GDP/GTP exchange on CDC42.

Kawasaki et al. (2007) found that ASEF2 was a GEF for both CDC42 and
RAC1 in MDCK and HeLa cells. Overexpression of ASEF2 increased membrane
ruffling and CDC42-mediated filopodia formation in HeLa cells.

Shen et al. (2008) showed that Nudel (NDEL1; 607538) colocalized with
Cdc42gap (ARHGAP1; 602732) at the leading edge of migrating NIH3T3 mouse
fibroblasts. This localization of Nudel required its phosphorylation by
Erk1 (MAPK3; 601795)/Erk2 (MAPK1; 176948). Shen et al. (2008) found that
Nudel competed with Cdc42 for binding Cdc42gap. Consequently, Nudel
inhibited Cdc42gap-mediated inactivation of Cdc42 in a dose-dependent
manner. Depletion of Nudel by RNA interference or overexpression of a
nonphosphorylatable Nudel mutant abolished Cdc42 activation and cell
migration. Shen et al. (2008) concluded that NUDEL facilitates cell
migration by sequestering CDC42GAP at the leading edge to stabilize
active CDC42 in response to extracellular stimuli.

Kang et al. (2008) performed a global characterization of rat neural
palmitoyl proteomes and identified most of the known neural palmitoyl
proteins, 68 in total, plus more than 200 novel palmitoyl protein
candidates, with further testing confirming palmitoylation for 21 of
these candidates. The novel palmitoyl proteins included neurotransmitter
receptors, transporters, adhesion molecules, scaffolding proteins, as
well as SNAREs and other vesicular trafficking proteins. Of particular
interest was the finding of palmitoylation for a brain-specific Cdc42
splice variant. The palmitoylated Cdc42 isoform (Cdc42-palm) differs
from the canonical, prenylated form (Cdc42-prenyl), with regard to both
localization and function: Cdc42-palm concentrates in dendritic spines
and has a special role in inducing these postsynaptic structures.
Furthermore, assessing palmitoylation dynamics in drug-induced activity
models identified rapidly induced changes for Cdc42 as well as for other
synaptic palmitoyl proteins, suggesting that palmitoylation may
participate broadly in the activity-driven changes that shape synapse
morphology and brain function.

Machacek et al. (2009) examined GTPase coordination in mouse embryonic
fibroblasts both through simultaneous visualization of 2 GTPase
biosensors and using a 'computational multiplexing' approach capable of
defining the relationships between multiple protein activities
visualized in separate experiments. They found that RhoA (165390) is
activated at the cell edge synchronous with edge advancement, whereas
Cdc42 and Rac1 are activated 2 microns behind the edge with a delay of
40 seconds. This indicates that Rac1 and RhoA operate antagonistically
through spatial separation and precise timing, and that RhoA has a role
in the initial events of protrusion, whereas Rac1 and Cdc42 activate
pathways implicated in reinforcement and stabilization of newly expanded
protrusions.

Frank et al. (2009) found that Cdc42 was involved in a signaling complex
that modulated presynaptic Cav2.1 (CACNA1A; 601011) calcium channels in
the Drosophila neuromuscular junction. This signaling system involved
the Rho-type GEF ephexin (NGEF; 605991), which appeared to act with
Cdc42 to activate the Eph receptor (see EPHA1; 179610) for modulation of
Cav2.1 channel activity.

Murakoshi et al. (2011) used 2-photon fluorescence lifetime imaging
microscopy to monitor the activity of 2 Rho GTPases, RhoA and Cdc42, in
single dendritic spines undergoing structural plasticity associated with
long-term potentiation in CA1 pyramidal neurons in cultured slices of
rat hippocampus. When long-term volume increase was induced in a single
spine using 2-photon glutamate uncaging, RhoA and Cdc42 were rapidly
activated in the stimulated spine. These activities decayed over about 5
minutes, and were then followed by a phase of persistent activation
lasting more than half an hour. Although active RhoA and Cdc42 were
similarly mobile, their activity patterns were different. RhoA
activation diffused out of the stimulated spine and spread over about 5
microns along the dendrite. In contrast, Cdc42 activation was restricted
to the stimulated spine, and exhibited a steep gradient at the spine
necks. Inhibition of the Rho-Rock pathway preferentially inhibited the
initial spine growth, whereas the inhibition of the Cdc42-Pak pathway
blocked the maintenance of sustained structural plasticity. RhoA and
Cdc42 activation depended on calcium ion/calmodulin-dependent kinase
(CaMKII). Thus, Murakoshi et al. (2011) concluded that RhoA and Cdc42
relay transient CaMKII activation to synapse-specific, long-term
signaling required for spine structural plasticity.

Using synthetic derivatives of the enteropathogenic Escherichia coli
guanine-nucleotide exchange factor Map, Orchard et al. (2012) found that
CDC42 GTPase signal transduction was controlled by interaction between
Map and the PDZ domains of EBP50 (SLC9A3R1; 604990) and the induction of
clusters of actin-rich membrane protrusions.

Keestra et al. (2013) demonstrated that NOD1 (605980) senses cytosolic
microbial products by monitoring the activation state of small Rho
GTPases. Activation of RAC1 (602048) and CDC42 by bacterial delivery or
ectopic expression of SopE, a virulence factor of the enteric pathogen
Salmonella, triggered the NOD1 signaling pathway with consequent RIP2
(603455)-mediated induction of NF-kappa-B (see 164011)-dependent
inflammatory responses. Similarly, activation of the NOD1 signaling
pathway by peptidoglycan required RAC1 activity. Furthermore, Keestra et
al. (2013) showed that constitutively active forms of RAC1, CDC42, and
RHOA (165390) activated the NOD1 signaling pathway.

Florian et al. (2013) reported an unexpected shift from canonical to
noncanonical Wnt signaling in mice due to elevated expression of Wnt5a
(164975) in aged hematopoietic stem cells (HSCs), which causes stem cell
aging. Wnt5a treatment of young HSCs induced aging-associated stem cell
apolarity, reduction of regenerative capacity, and an aging-like
myeloid-lymphoid differentiation skewing via activation of the small Rho
GTPase Cdc42. Conversely, Wnt5a haploinsufficiency attenuated HSC aging,
whereas stem cell-intrinsic reduction of Wnt5a expression resulted in
functionally rejuvenated aged HSCs. Florian et al. (2013) concluded that
the data demonstrated a critical role for stem cell-intrinsic
noncanonical Wnt5a signaling in HSC aging.

GENE STRUCTURE

Nicole et al. (1999) determined the organization of the CDC42 gene and
found that the gene encodes the placental and brain isoforms generated
by alternative splicing.

Moats-Staats and Stiles (1995) showed that the 5-prime end of another
gene, called BB1 by them (601106), overlaps the 3-prime end of G25K.

BIOCHEMICAL FEATURES

- Crystal Structure

Through a structural analysis of DOCK9 (607325)-CDC42 complexes, Yang et
al. (2009) identified a nucleotide sensor within the alpha-10 helix of
the DHR2 domain that contributes to release of guanine diphosphate (GDP)
and then to discharge of the activated GTP-bound Cdc42. Magnesium
exclusion, a critical factor in promoting GDP release, is mediated by a
conserved valine residue within this sensor, whereas binding of
GTP-magnesium ion to the nucleotide-free complex results in
magnesium-inducing displacement of the sensor to stimulate discharge of
Cdc42-GTP. Yang et al. (2009) concluded that their studies identified an
unusual mechanism of GDP release and defined the complete guanine
nucleotide exchange factor catalytic cycle from GDP dissociation
followed by GTP binding and discharge of the activated GTPase.

MAPPING

Using SSCP analysis of a mouse backcross panel, Marks and Kwiatkowski
(1996) demonstrated that the gene encoding cdc42 is localized to the
distal portion of mouse chromosome 4 between Ephb2 proximally and Cappb
(601572) distally. The human homologs of both of the 2 flanking genes
were mapped to human chromosome 1p36.1 by Barron-Casella et al. (1995),
thus indicating that this is the likely site of the human CDC42 gene.
The CDC42 gene was mapped to the 1p36-p35 region by radiation hybrid
analysis (Schuler et al., 1996; Jensen et al., 1997; Deloukas et al.,
1998).

Nicole et al. (1999) demonstrated a CDC42-like transcript on chromosome
4 that does not contain introns and is similar to the placental isoform,
suggesting that it is a processed pseudogene.

Nicole et al. (1999) excluded the CDC42 gene as the site of mutation in
the Schwartz-Jampel syndrome type 1 (255800).

ANIMAL MODEL

Wu et al. (2006) stated that constitutive knockout of Cdc42 in mice
results in death around implantation. In order to examine the role of
Cdc42 in the differentiation of skin stem cells into hair follicles,
they targeted Cdc42 deletion to keratinocytes. Mutant mice were born
without obvious defects but showed impaired hair formation and growth
retardation. Within 4 weeks, all hairs were lost and did not grow again
in older animals. In the absence of Cdc42, degradation of beta-catenin
(CTNNB1; 116806) increased corresponding to decreased phosphorylation of
Gsk3-beta and increased phosphorylation of axin (603816), which is
required for binding of beta-catenin to the degradation machinery. Wu et
al. (2006) concluded that Cdc42 regulation of beta-catenin turnover is
required for terminal differentiation of hair follicle progenitor cells.

By targeted deletion of Cdc42 in telencephalic neural progenitors in
mouse embryos, Chen et al. (2006) found that Cdc42 was essential for
establishment of apical-basal polarity of the telencephalic
neuroepithelium, a necessity for expansion and bifurcation of cerebral
hemispheres.

*FIELD* RF
1. Barron-Casella, E. A.; Torres, M. A.; Scherer, S. W.; Heng, H.
H.; Tsui, L. C.; Casella, J. F.: Sequence analysis and chromosomal
localization of human Cap Z: conserved residues within the actin-binding
domain may link Cap Z to gelsolin/severin and profilin protein families. J.
Biol. Chem. 270: 21472-21479, 1995.

2. Brown, J. L.; Stowers, L.; Baer, M.; Trejo, J.; Coughlin, S.; Chant,
J.: Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase
pathway. Curr. Biol. 6: 598-605, 1996.

3. Chen, L.; Liao, G.; Yang, L.; Campbell, K.; Nakafuku, M.; Kuan,
C.-Y.; Zheng, Y.: Cdc42 deficiency causes Sonic hedgehog-independent
holoprosencephaly. Proc. Nat. Acad. Sci. 16520-16525, 2006.

4. Deloukas, P.; Schuler, G. D.; Gyapay, G.; Beasley, E. M.; Soderlund,
C.; Rodriguez-Tome, P.; Hui, L.; Matise, T. C.; McKusick, K. B.; Beckmann,
J. S.; Bentolila, S.; Bihoreau, M.-T.; and 53 others: A physical
map of 30,000 human genes. Science 282: 744-746, 1998.

5. Erickson, J. W.; Zhang, C.; Kahn, R. A.; Evans, T.; Cerione, R.
A.: Mammalian cdc42 is a brefeldin A-sensitive component of the Golgi
apparatus. J. Biol. Chem. 271: 26850-26854, 1996.

6. Etienne-Manneville, S.; Hall, A.: Cdc42 regulates GSK-3-beta and
adenomatous polyposis coli to control cell polarity. Nature 421:
753-756, 2003.

7. Florian, M. C.; Nattamai, K. J.; Dorr, K.; Marka, G.; Uberle, B.;
Vas, V.; Eckl, C.; Andra, I.; Schiemann, M.; Oostendorp, R. A. J.;
Scharffetter-Kochanek, K.; Kestler, H. A.; Zheng, Y.; Geiger, H.:
A canonical to non-canonical Wnt signalling switch in haematopoietic
stem-cell ageing. Nature 503: 392-396, 2013.

8. Frank, C. A.; Pielage, J.; Davis, G. W.: A presynaptic homeostatic
signaling system composed of the Eph receptor, Ephexin, Cdc42, and
Cav2.1 calcium channels. Neuron 61: 556-569, 2009.

9. Garrett, W. S.; Chen, L.-M.; Kroschewski, R.; Ebersold, M.; Turley,
S.; Trombetta, S.; Galan, J. E.; Mellman, I.: Developmental control
of endocytosis in dendritic cells by Cdc42. Cell 102: 325-334, 2000.

10. Hamann, M. J.; Lubking, C. M.; Luchini, D. N.; Billadeau, D. D.
: Asef2 functions as a Cdc42 exchange factor and is stimulated by
the release of an autoinhibitory module from a concealed C-terminal
activation element. Molec. Cell. Biol. 27: 1380-1393, 2007.

11. Irie, F.; Yamaguchi, Y.: EphB receptors regulate dendritic spine
development via intersectin, Cdc42 and N-WASP. Nature Neurosci. 5:
1117-1118, 2002.

12. Jensen, S. J.; Sulman, E. P.; Maris, J. M.; Matise, T. C.; Vojta,
P. J.; Barrett, J. C.; Brodeur, G. M.; White, P. S.: An integrated
transcript map of human chromosome 1p35-p36. Genomics 42: 126-136,
1997.

13. Kang, R.; Wan, J.; Arstikaitis, P.; Takahashi, H.; Huang, K.;
Bailey, A. O.; Thompson, J. X.; Roth, A. F.; Drisdel, R. C.; Mastro,
R.; Green, W. N.; Yates, J. R., III; Davis, N. G.; El-Husseini, A.
: Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation. Nature 456:
904-909, 2008.

14. Kawasaki, Y.; Sagara, M.; Shibata, Y.; Shirouzu, M.; Yokoyama,
S.; Akiyama, T.: Identification and characterization of Asef2, a
guanine-nucleotide exchange factor specific for Rac1 and Cdc42. Oncogene 26:
7620-7627, 2007.

15. Keestra, A. M.; Winter, M. G.; Auburger, J. J.; Frassle, S. P.;
Xavier, M. N.; Winter, S. E.; Kim, A.; Poon, V.; Ravesloot, M. M.;
Waldenmaier, J. F. T.; Tsolis, R. M.; Eigenheer, R. A.; Baumler, A.
J.: Manipulation of small Rho GTPases is a pathogen-induced process
detected by NOD1. Nature 496: 233-237, 2013.

16. Kim, A. S.; Kakalis, L. T.; Abdul-Manan, N.; Liu, G. A.; Rosen,
M. K.: Autoinhibition and activation mechanisms of the Wiskott-Aldrich
syndrome protein. Nature 404: 151-158, 2000.

17. Machacek, M.; Hodgson, L.; Welch, C.; Elliott, H.; Pertz, O.;
Nalbant, P.; Abell, A.; Johnson, G. L.; Hahn, K. M.; Danuser, G.:
Coordination of Rho GTPase activities during cell protrusion. Nature 461:
99-103, 2009.

18. Manser, E.; Leung, T.; Salihuddin, H.; Tan, L.; Lim, L.: A non-receptor
tyrosine kinase that inhibits the GTPase activity of p21cdc42. Nature 363:
364-367, 1993.

19. Manser, E.; Leung, T.; Salihuddin, H.; Zhao, Z.; Lim, L.: A brain
serine/threonine protein kinase activated by Cdc42 and Rac1. Nature 367:
40-46, 1994.

20. Marks, P. W.; Kwiatkowski, D. J.: Genomic organization and chromosomal
location of murine Cdc42. Genomics 38: 13-18, 1996.

21. Martin-Belmonte, F.; Gassama, A.; Datta, A.; Yu, W.; Rescher,
U.; Gerke, V.; Mostov, K.: PTEN-mediated apical segregation of phosphoinositides
controls epithelial morphogenesis through Cdc42. Cell 128: 383-397,
2007.

22. Moats-Staats, B. M.; Stiles, A. D.: Southern hybridization analyses
of somatic cell hybrids reveal that human BB1 is a member of a multigene
family dispersed throughout the human genome and appears to be linked
to the human G25K genes. DNA Cell Biol. 14: 465-474, 1995.

23. Munemitsu, S.; Innis, M. A.; Clark, R.; McCormick, F.; Ullrich,
A.; Polakis, P.: Molecular cloning and expression of a G25K cDNA,
the human homolog of the yeast cell cycle gene CDC42. Molec. Cell.
Biol. 10: 5977-5982, 1990.

24. Murakoshi, H.; Wang, H.; Yasuda, R.: Local, persistent activation
of Rho GTPases during plasticity of single dendritic spines. Nature 472:
100-104, 2011.

25. Musch, A.; Cohen, D.; Kreitzer, G.; Rodriguez-Boulan, E.: cdc42
regulates the exit of apical and basolateral proteins from the trans-Golgi
network. EMBO J. 20: 2171-2179, 2001.

26. Nakaya, Y.; Kuroda, S.; Katagiri, Y. T.; Kaibuchi, K.; Takahashi,
Y.: Mesenchymal-epithelial transition during somitic segmentation
is regulated by differential roles of Cdc42 and Rac1. Dev. Cell 7:
425-438, 2004.

27. Nalbant, P.; Hodgson, L.; Kraynov, V.; Toutchkine, A.; Hahn, K.
M.: Activation of endogenous Cdc42 visualized in living cells. Science 305:
1615-1619, 2004.

28. Nicole, S.; White, P. S.; Topaloglu, H.; Beigthon, P.; Salih,
M.; Hentati, F.; Fontaine, B.: The human CDC42 gene: genomic organization,
evidence for the existence of a putative pseudogene and exclusion
as a SJS1 candidate gene. Hum. Genet. 105: 98-103, 1999.

29. Orchard, R. C.; Kittisopikul, M.; Altschuler, S. J.; Wu, L. F.;
Suel, G. M.; Alto, N. M.: Identification of F-actin as the dynamic
hub in a microbial-induced GTPase polarity circuit. Cell 148: 803-815,
2012.

30. Schuler, G. D.; Boguski, M. S.; Stewart, E. A.; Stein, L. D.;
Gyapay, G.; Rice, K.; White, R. E.; Rodriguez-Tome, P.; Aggarwal,
A.; Bajorek, E.; Bentolila, S.; Birren, B. B.; and 92 others: A
gene map of the human genome. Science 274: 540-546, 1996.

31. Shen, Y.; Li, N.; Wu, S.; Zhou, Y.; Shan, Y.; Zhang, Q.; Ding,
C.; Yuan, Q.; Zhao, F.; Zeng, R.; Zhu, X.: Nudel binds Cdc42GAP to
modulate Cdc42 activity at the leading edge of migrating cells. Dev.
Cell 14: 342-353, 2008.

32. Shinjo, K.; Koland, J. G.; Hart, M. J.; Narasimhan, V.; Johnson,
D. I.; Evans, T.; Cerione, R. A.: Molecular cloning of the gene for
the human placental GTP-binding protein G(p) (G25K): identification
of this GTP-binding protein as the human homolog of the yeast cell-division-cycle
protein CDC42. Proc. Nat. Acad. Sci. 87: 9853-9857, 1990.

33. Sin, W. C.; Haas, K.; Ruthazer, E. S.; Cline, H. T.: Dendrite
growth increased by visual activity requires NMDA receptor and Rho
GTPases. Nature 419: 475-480, 2002.

34. Wells, C. D.; Fawcett, J. P.; Traweger, A.; Yamanaka, Y.; Goudreault,
M.; Elder, K.; Kulkarni, S.; Gish, G.; Virag, C.; Lim, C.; Colwill,
K.; Starostine, A.; Metalnikov, P.; Pawson, T.: A Rich1/Amot complex
regulates the Cdc42 GTPase and apical-polarity proteins in epithelial
cells. Cell 125: 535-548, 2006.

35. Wu, W. J.; Erickson, J. W.; Lin, R.; Cerione, R. A.: The gamma-subunit
of the coatomer complex binds Cdc42 to mediate transformation. Nature 405:
800-804, 2000.

36. Wu, W. J.; Tu, S.; Cerione, R. A.: Activated Cdc42 sequesters
c-Cbl and prevents EGF receptor degradation. Cell 114: 715-725,
2003.

37. Wu, X.; Quondamatteo, F.; Lefever, T.; Czuchra, A.; Meyer, H.;
Chrostek, A.; Paus, R.; Langbein, L.; Brakebusch, C.: Cdc42 controls
progenitor cell differentiation and beta-catenin turnover in skin. Genes
Dev. 20: 571-585, 2006.

38. Yang, J.; Zhang, Z.; Roe, S. M.; Marshall, C. J.; Barford, D.
: Activation of Rho GTPases by DOCK exchange factors is mediated by
a nucleotide sensor. Science 325: 1398-1402, 2009.

39. Yasuda, S.; Oceguera-Yanez, F.; Kato, T.; Okamoto, M.; Yonemura,
S.; Terada, Y.; Ishizaki, T.; Narumiya, S.: Cdc42 and mDia3 regulate
microtubule attachment to kinetochores. Nature 428: 767-771, 2004.

40. Zheng, Y.; Fischer, D. J.; Santos, M. F.; Tigyi, G.; Pasteris,
N. G.; Gorski, J. L.; Xu, Y.: The faciogenital dysplasia gene product
FGD1 functions as a Cdc42Hs-specific guanine-nucleotide exchange factor. J.
Biol. Chem. 271: 33169-33172, 1996.

*FIELD* CN
Ada Hamosh - updated: 12/09/2013
Ada Hamosh - updated: 5/6/2013
Paul J. Converse - updated: 10/26/2012
Matthew B. Gross - updated: 5/10/2011
Ada Hamosh - updated: 5/9/2011
Patricia A. Hartz - updated: 1/6/2011
Matthew B. Gross - updated: 5/11/2010
Ada Hamosh - updated: 1/8/2010
Ada Hamosh - updated: 10/13/2009
Ada Hamosh - updated: 2/18/2009
Patricia A. Hartz - updated: 4/28/2008
Patricia A. Hartz - updated: 8/30/2007
Patricia A. Hartz - updated: 1/19/2007
Patricia A. Hartz - updated: 5/3/2006
Patricia A. Hartz - updated: 3/28/2006
Patricia A. Hartz - updated: 10/7/2004
Ada Hamosh - updated: 9/28/2004
Ada Hamosh - updated: 4/16/2004
Cassandra L. Kniffin - updated: 3/5/2003
Ada Hamosh - updated: 1/29/2003
Patricia A. Hartz - updated: 6/5/2002
Stylianos E. Antonarakis - updated: 9/7/2000
Ada Hamosh - updated: 7/20/2000
Ada Hamosh - updated: 3/10/2000
Victor A. McKusick - updated: 8/23/1999
Jennifer P. Macke - updated: 4/8/1998
Jennifer P. Macke - updated: 5/28/1997
Alan F. Scott - updated: 3/6/1996

*FIELD* CD
Victor A. McKusick: 1/17/1991

*FIELD* ED
alopez: 12/09/2013
alopez: 5/6/2013
mgross: 11/20/2012
terry: 10/26/2012
mgross: 5/10/2011
alopez: 5/10/2011
terry: 5/9/2011
mgross: 1/24/2011
terry: 1/6/2011
wwang: 5/17/2010
mgross: 5/11/2010
alopez: 1/11/2010
terry: 1/8/2010
alopez: 10/22/2009
terry: 10/13/2009
carol: 7/7/2009
alopez: 2/20/2009
terry: 2/18/2009
mgross: 4/28/2008
ckniffin: 2/5/2008
mgross: 10/4/2007
terry: 8/30/2007
mgross: 1/19/2007
mgross: 6/7/2006
terry: 5/3/2006
wwang: 4/3/2006
terry: 3/28/2006
mgross: 10/7/2004
alopez: 10/4/2004
tkritzer: 9/28/2004
alopez: 4/19/2004
terry: 4/16/2004
cwells: 11/10/2003
tkritzer: 3/14/2003
ckniffin: 3/5/2003
alopez: 3/3/2003
alopez: 1/29/2003
terry: 1/29/2003
alopez: 11/19/2002
terry: 11/18/2002
carol: 6/5/2002
terry: 11/15/2001
mgross: 9/7/2000
alopez: 7/20/2000
alopez: 3/10/2000
mcapotos: 12/7/1999
psherman: 11/3/1999
psherman: 10/18/1999
jlewis: 9/3/1999
terry: 8/23/1999
kayiaros: 7/13/1999
psherman: 3/18/1999
psherman: 4/21/1998
dholmes: 4/8/1998
alopez: 8/1/1997
alopez: 7/23/1997
mark: 12/16/1996
terry: 12/10/1996
terry: 4/17/1996
mark: 3/6/1996
carol: 4/1/1994
supermim: 3/16/1992
carol: 1/2/1992
carol: 3/4/1991
carol: 1/17/1991