CDC42_HUMAN
ID CDC42_HUMAN Reviewed; 191 AA.
AC P60953; P21181; P25763; Q7L8R5; Q9UDI2;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 2.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Cell division control protein 42 homolog {ECO:0000305};
DE EC=3.6.5.2 {ECO:0000269|PubMed:21565175, ECO:0000269|PubMed:23940119};
DE AltName: Full=G25K GTP-binding protein;
DE Flags: Precursor;
GN Name=CDC42 {ECO:0000312|HGNC:HGNC:1736};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=2122236; DOI=10.1128/mcb.10.11.5977-5982.1990;
RA Munemitsu S., Innis M.A., Clark R., McCormick F., Ullrich A., Polakis P.;
RT "Molecular cloning and expression of a G25K cDNA, the human homolog of the
RT 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., Evans T.,
RA Cerione R.A.;
RT "Molecular cloning of the gene for the human placental GTP-binding protein
RT Gp (G25K): identification of this GTP-binding protein as the human homolog
RT 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 sequenced by
RT 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., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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 project:
RT 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 (ISOFORM
RP 1), AND IDENTIFICATION BY 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 ARHGDIB.
RX PubMed=7512369; DOI=10.1002/gcc.2870080408;
RA Adra C.N., Ko J., Leonard D., Wirth L.J., Cerione R.A., Lim B.;
RT "Identification of a novel protein with GDP dissociation inhibitor activity
RT for the ras-like proteins CDC42Hs and rac I.";
RL Genes Chromosomes Cancer 8:253-261(1993).
RN [12]
RP GLYCOSYLATION AT THR-35 (MICROBIAL INFECTION).
RX PubMed=7777059; DOI=10.1038/375500a0;
RA Just I., Selzer J., Wilm M., von Eichel-Streiber C., Mann M., Aktories K.;
RT "Glucosylation of Rho proteins by Clostridium difficile toxin B.";
RL Nature 375:500-503(1995).
RN [13]
RP GLYCOSYLATION AT THR-35 (MICROBIAL INFECTION).
RX PubMed=7775453; DOI=10.1074/jbc.270.23.13932;
RA Just I., Wilm M., Selzer J., Rex G., von Eichel-Streiber C., Mann M.,
RA Aktories K.;
RT "The enterotoxin from Clostridium difficile (ToxA) monoglucosylates the Rho
RT proteins.";
RL J. Biol. Chem. 270:13932-13936(1995).
RN [14]
RP GLYCOSYLATION AT THR-35 (MICROBIAL INFECTION).
RX PubMed=8810274; DOI=10.1074/jbc.271.41.25173;
RA Selzer J., Hofmann F., Rex G., Wilm M., Mann M., Just I., Aktories K.;
RT "Clostridium novyi alpha-toxin-catalyzed incorporation of GlcNAc into Rho
RT subfamily proteins.";
RL J. Biol. Chem. 271:25173-25177(1996).
RN [15]
RP INTERACTION WITH CDC42EP1; CDC42EP2; CDC42EP3 AND CDC42EP5.
RC TISSUE=Embryo;
RX PubMed=10490598; DOI=10.1128/mcb.19.10.6585;
RA Joberty G., Perlungher R.R., Macara I.G.;
RT "The Borgs, a new family of Cdc42 and TC10 GTPase-interacting proteins.";
RL Mol. Cell. Biol. 19:6585-6597(1999).
RN [16]
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 [17]
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 [18]
RP INTERACTION WITH PARD6A, AND MUTAGENESIS OF GLY-12.
RX PubMed=10954424; DOI=10.1242/jcs.113.18.3267;
RA Johansson A.-S., Driessens M., Aspenstroem P.;
RT "The mammalian homologue of the Caenorhabditis elegans polarity protein
RT PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1.";
RL J. Cell Sci. 113:3267-3275(2000).
RN [19]
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 regulation
RT of membrane ruffling.";
RL Nature 408:732-735(2000).
RN [20]
RP INTERACTION WITH PARD6A; PARD6B AND PARD6G, SUBUNIT OF A COMPLEX CONTAINING
RP 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 PAR6
RT as an adaptor that links the small GTPases Rac and Cdc42 to atypical
RT protein kinase C.";
RL Genes Cells 6:107-119(2001).
RN [21]
RP INTERACTION WITH ITGB1BP1.
RX PubMed=11807099; DOI=10.1083/jcb.200108030;
RA Degani S., Balzac F., Brancaccio M., Guazzone S., Retta S.F., Silengo L.,
RA 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 [22]
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., 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 [23]
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 the
RT Src tyrosine kinase.";
RL J. Biol. Chem. 278:49293-49300(2003).
RN [24]
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 for Rho
RT GTPases Cdc42 and Rac1 and stimulates actin remodeling.";
RL Mol. Cell. Biol. 23:2151-2161(2003).
RN [25]
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 hippocampal
RT neurons by specific acylated protein motifs.";
RL Mol. Biol. Cell 15:2205-2217(2004).
RN [26]
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 [27]
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 p130Cas.";
RL J. Biol. Chem. 281:37527-37535(2006).
RN [28]
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., Tanaka H.,
RA 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 [29]
RP AMPYLATION AT TYR-32 (MICROBIAL INFECTION), 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., Mendez J.C.,
RA 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 [30]
RP INTERACTION WITH FNBP1L.
RX PubMed=19798448; DOI=10.1371/journal.pgen.1000675;
RA Giuliani C., Troglio F., Bai Z., Patel F.B., Zucconi A., Malabarba M.G.,
RA Disanza A., Stradal T.B., Cassata G., Confalonieri S., Hardin J.D.,
RA Soto M.C., Grant B.D., Scita G.;
RT "Requirements for F-BAR proteins TOCA-1 and TOCA-2 in actin dynamics and
RT membrane trafficking during Caenorhabditis elegans oocyte growth and
RT embryonic epidermal morphogenesis.";
RL PLoS Genet. 5:E1000675-E1000675(2009).
RN [31]
RP AMPYLATION AT THR-35 (MICROBIAL INFECTION).
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 and
RT downstream signaling.";
RL Science 323:269-272(2009).
RN [32]
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., Santana Bernachi J.,
RA Paes Leme A.F., Kobarg J.;
RT "Characterization of hNek6 interactome reveals an important role for its
RT short N-terminal domain and colocalization with proteins at the
RT centrosome.";
RL J. Proteome Res. 9:6298-6316(2010).
RN [33]
RP CATALYTIC ACTIVITY.
RX PubMed=21565175; DOI=10.1016/j.bbrc.2011.04.116;
RA Naji L., Pacholsky D., Aspenstrom P.;
RT "ARHGAP30 is a Wrch-1-interacting protein involved in actin dynamics and
RT cell adhesion.";
RL Biochem. Biophys. Res. Commun. 409:96-102(2011).
RN [34]
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., Buerckstuemmer T.,
RA 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 [35]
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., 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 [36]
RP CATALYTIC ACTIVITY.
RX PubMed=23940119; DOI=10.1083/jcb.201304133;
RA Dubash A.D., Koetsier J.L., Amargo E.V., Najor N.A., Harmon R.M.,
RA Green K.J.;
RT "The GEF Bcr activates RhoA/MAL signaling to promote keratinocyte
RT differentiation via desmoglein-1.";
RL J. Cell Biol. 202:653-666(2013).
RN [37]
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 [38]
RP GLYCOSYLATION AT TYR-32 (MICROBIAL INFECTION).
RX PubMed=24141704; DOI=10.1038/nsmb.2688;
RA Jank T., Bogdanovic X., Wirth C., Haaf E., Spoerner M., Boehmer K.E.,
RA Steinemann M., Orth J.H., Kalbitzer H.R., Warscheid B., Hunte C.,
RA Aktories K.;
RT "A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation
RT of Gq and Gi proteins.";
RL Nat. Struct. Mol. Biol. 20:1273-1280(2013).
RN [39]
RP GLYCOSYLATION AT THR-35 (MICROBIAL INFECTION).
RX PubMed=24905543; DOI=10.1111/cmi.12321;
RA Genth H., Pauillac S., Schelle I., Bouvet P., Bouchier C.,
RA Varela-Chavez C., Just I., Popoff M.R.;
RT "Haemorrhagic toxin and lethal toxin from Clostridium sordellii strain
RT vpi9048: molecular characterization and comparative analysis of substrate
RT specificity of the large clostridial glucosylating toxins.";
RL Cell. Microbiol. 16:1706-1721(2014).
RN [40]
RP FUNCTION.
RX PubMed=26465210; DOI=10.1038/ncomms9623;
RA Schlam D., Bagshaw R.D., Freeman S.A., Collins R.F., Pawson T., Fairn G.D.,
RA Grinstein S.;
RT "Phosphoinositide 3-kinase enables phagocytosis of large particles by
RT terminating actin assembly through Rac/Cdc42 GTPase-activating proteins.";
RL Nat. Commun. 6:8623-8623(2015).
RN [41]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [42]
RP FUNCTION.
RX PubMed=33523862; DOI=10.1126/sciadv.abe1386;
RA Majmundar A.J., Buerger F., Forbes T.A., Klaembt V., Schneider R.,
RA Deutsch K., Kitzler T.M., Howden S.E., Scurr M., Tan K.S., Krzeminski M.,
RA Widmeier E., Braun D.A., Lai E., Ullah I., Amar A., Kolb A., Eddy K.,
RA Chen C.H., Salmanullah D., Dai R., Nakayama M., Ottlewski I.,
RA Kolvenbach C.M., Onuchic-Whitford A.C., Mao Y., Mann N., Nabhan M.M.,
RA Rosen S., Forman-Kay J.D., Soliman N.A., Heilos A., Kain R., Aufricht C.,
RA Mane S., Lifton R.P., Shril S., Little M.H., Hildebrandt F.;
RT "Recessive NOS1AP variants impair actin remodeling and cause glomerulopathy
RT in humans and mice.";
RL Sci. Adv. 7:0-0(2021).
RN [43]
RP STRUCTURE BY NMR.
RX PubMed=9220962; DOI=10.1021/bi970694x;
RA Feltham J.L., Dotsch V., Raza S., Manor D., Cerione R.A., Sutcliffe M.J.,
RA Wagner G., Oswald R.E.;
RT "Definition of the switch surface in the solution structure of Cdc42Hs.";
RL Biochemistry 36:8755-8766(1997).
RN [44]
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 [45]
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., Laue E.,
RA 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 [46]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF VAL-12 MUTANT.
RX PubMed=10211824; DOI=10.1110/ps.8.4.778;
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 states
RT in one crystal.";
RL Protein Sci. 8:778-787(1999).
RN [47]
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 [48] {ECO:0007744|PDB:1DOA}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1-188, ISOPRENYLATION AT CYS-188,
RP AND METHYLATION AT CYS-188.
RX PubMed=10676816; DOI=10.1016/s0092-8674(00)80670-4;
RA Hoffman G.R., Nassar N., Cerione R.A.;
RT "Structure of the Rho family GTP-binding protein Cdc42 in complex with the
RT multifunctional regulator RhoGDI.";
RL Cell 100:345-356(2000).
RN [49]
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 [50]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-181 IN COMPLEX WITH H.SOMNUS
RP IBPA AND GDP, AND AMPYLATION AT TYR-32 (MICROBIAL INFECTION).
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).
RN [51]
RP X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 1-188 IN COMPLEX WITH MOUSE
RP DOCK8, AND ACTIVITY REGULATION.
RX PubMed=22461490; DOI=10.1182/blood-2012-01-407098;
RA Harada Y., Tanaka Y., Terasawa M., Pieczyk M., Habiro K., Katakai T.,
RA Hanawa-Suetsugu K., Kukimoto-Niino M., Nishizaki T., Shirouzu M., Duan X.,
RA Uruno T., Nishikimi A., Sanematsu F., Yokoyama S., Stein J.V., Kinashi T.,
RA Fukui Y.;
RT "DOCK8 is a Cdc42 activator critical for interstitial dendritic cell
RT migration during immune responses.";
RL Blood 119:4451-4461(2012).
RN [52]
RP INVOLVEMENT IN TKS, AND VARIANT TKS CYS-64.
RX PubMed=26386261; DOI=10.1002/ajmg.a.37275;
RA Takenouchi T., Kosaki R., Niizuma T., Hata K., Kosaki K.;
RT "Macrothrombocytopenia and developmental delay with a de novo CDC42
RT mutation: Yet another locus for thrombocytopenia and developmental delay.";
RL Am. J. Med. Genet. A 167A:2822-2825(2015).
RN [53]
RP VARIANT TKS CYS-64.
RX PubMed=26708094; DOI=10.1002/ajmg.a.37526;
RA Takenouchi T., Okamoto N., Ida S., Uehara T., Kosaki K.;
RT "Further evidence of a mutation in CDC42 as a cause of a recognizable
RT syndromic form of thrombocytopenia.";
RL Am. J. Med. Genet. A 170:852-855(2016).
CC -!- FUNCTION: Plasma membrane-associated small GTPase which cycles between
CC an active GTP-bound and an inactive GDP-bound state. In active state
CC binds to a variety of effector proteins to regulate cellular responses.
CC Involved in epithelial cell polarization processes. Regulates the
CC bipolar attachment of spindle microtubules to kinetochores before
CC chromosome congression in metaphase (PubMed:15642749). Regulates cell
CC migration (PubMed:17038317). In neurons, plays a role in the extension
CC and maintenance of the formation of filopodia, thin and actin-rich
CC surface projections (PubMed:14978216). Required for DOCK10-mediated
CC spine formation in Purkinje cells and hippocampal neurons. In
CC podocytes, facilitates filopodia and podosomes formation upon DOCK11-
CC activation (PubMed:33523862). Upon activation by CaMKII, modulates
CC dendritic spine structural plasticity by relaying CaMKII transient
CC activation to synapse-specific, long-term signaling (By similarity).
CC Also plays a role in phagocytosis through organization of the F-actin
CC cytoskeleton associated with forming phagocytic cups (PubMed:26465210).
CC {ECO:0000250|UniProtKB:P60766, ECO:0000250|UniProtKB:Q8CFN2,
CC ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:15642749,
CC ECO:0000269|PubMed:17038317, ECO:0000269|PubMed:26465210,
CC ECO:0000269|PubMed:33523862}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000269|PubMed:21565175, ECO:0000269|PubMed:23940119};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000305|PubMed:21565175, ECO:0000305|PubMed:23940119};
CC -!- ACTIVITY REGULATION: Regulated by guanine nucleotide exchange factors
CC (GEFs) which promote the exchange of bound GDP for free GTP, GTPase
CC activating proteins (GAPs) which increase the GTP hydrolysis activity,
CC and GDP dissociation inhibitors which inhibit the dissociation of the
CC nucleotide from the GTPase. {ECO:0000269|PubMed:12172552}.
CC -!- SUBUNIT: Interacts with CDC42EP1, CDC42EP2, CDC42EP3, CDC42EP4,
CC CDC42EP5, CDC42SE1, CDC42SE2, PARD6A, PARD6B and PARD6G (in a GTP-
CC dependent manner) (PubMed:10490598, PubMed:10816584, PubMed:10954424,
CC PubMed:11260256). Interacts with activated CSPG4 and with BAIAP2
CC (PubMed:10587647, PubMed:11130076). Interacts with activated CSPG4 and
CC with BAIAP2 (By similarity). Interacts with DOCK11/Zizimin2; the
CC interaction activates CDC42 by exchanging GDP for GTP (By similarity).
CC Interacts with DOCK9; the interaction activates CDC42 by exchanging GDP
CC for GTP (PubMed:12172552, PubMed:19745154). Interacts with DOCK8 (via
CC DHR-2 domain); the interaction activates CDC42 by exchanging GDP for
CC GTP (PubMed:12172552). Interacts with IQGAP1 (By similarity). Interacts
CC with NET1 and ARHGAP33/TCGAP (By similarity). Part of a complex with
CC PARD3, PARD6A or PARD6B and PRKCI or PRKCZ (PubMed:11260256). The GTP-
CC bound form interacts with CCPG1 (By similarity). Interacts with USP6
CC (PubMed:12612085). Interacts with NEK6 (PubMed:20873783). Part of a
CC collagen stimulated complex involved in cell migration composed of
CC CDC42, CRK, TNK2 and BCAR1/p130cas (PubMed:17038317). Interacts with
CC ITGB1BP1 (PubMed:11807099). Interacts with ARHGDIA; this interaction
CC inactivates and stabilizes CDC42 (PubMed:23434736). Interacts with
CC ARHGDIB; this maintains CDC42 in the inactive, GDP-bound form
CC (PubMed:7512369). Interacts (in GTP-bound form) with FNBP1L and ABI1,
CC but only in the presence of FNBP1L (PubMed:19798448). May interact with
CC ARHGEF16; responsible for the activation of CDC42 by the viral protein
CC HPV16 E6 (PubMed:21139582). {ECO:0000250|UniProtKB:P60766,
CC ECO:0000269|PubMed:10490598, ECO:0000269|PubMed:10587647,
CC ECO:0000269|PubMed:10816584, ECO:0000269|PubMed:10954424,
CC ECO:0000269|PubMed:11130076, ECO:0000269|PubMed:11260256,
CC ECO:0000269|PubMed:11807099, ECO:0000269|PubMed:12172552,
CC ECO:0000269|PubMed:12612085, ECO:0000269|PubMed:17038317,
CC ECO:0000269|PubMed:19745154, ECO:0000269|PubMed:19798448,
CC ECO:0000269|PubMed:20873783, ECO:0000269|PubMed:21139582,
CC ECO:0000269|PubMed:22461490, ECO:0000269|PubMed:23434736,
CC ECO:0000269|PubMed:7512369}.
CC -!- INTERACTION:
CC P60953; O95477: ABCA1; NbExp=2; IntAct=EBI-81752, EBI-784112;
CC P60953; P25054: APC; NbExp=9; IntAct=EBI-81752, EBI-727707;
CC P60953; P52565: ARHGDIA; NbExp=4; IntAct=EBI-81752, EBI-712693;
CC P60953; Q9UQB8: BAIAP2; NbExp=2; IntAct=EBI-81752, EBI-525456;
CC P60953; Q9UQB8-4: BAIAP2; NbExp=4; IntAct=EBI-81752, EBI-6174091;
CC P60953; P60953: CDC42; NbExp=2; IntAct=EBI-81752, EBI-81752;
CC P60953; Q5VT25: CDC42BPA; NbExp=5; IntAct=EBI-81752, EBI-689171;
CC P60953; Q00587: CDC42EP1; NbExp=8; IntAct=EBI-81752, EBI-744130;
CC P60953; Q00587-2: CDC42EP1; NbExp=3; IntAct=EBI-81752, EBI-11027409;
CC P60953; O14613: CDC42EP2; NbExp=10; IntAct=EBI-81752, EBI-3438291;
CC P60953; Q8WUI4-6: HDAC7; NbExp=3; IntAct=EBI-81752, EBI-12094670;
CC P60953; P46940: IQGAP1; NbExp=11; IntAct=EBI-81752, EBI-297509;
CC P60953; Q5S007: LRRK2; NbExp=3; IntAct=EBI-81752, EBI-5323863;
CC P60953; Q16584: MAP3K11; NbExp=3; IntAct=EBI-81752, EBI-49961;
CC P60953; Q96L34: MARK4; NbExp=2; IntAct=EBI-81752, EBI-302319;
CC P60953; Q13153: PAK1; NbExp=12; IntAct=EBI-81752, EBI-1307;
CC P60953; Q13177: PAK2; NbExp=8; IntAct=EBI-81752, EBI-1045887;
CC P60953; O96013: PAK4; NbExp=4; IntAct=EBI-81752, EBI-713738;
CC P60953; Q9P286: PAK5; NbExp=5; IntAct=EBI-81752, EBI-741896;
CC P60953; Q9NQU5: PAK6; NbExp=4; IntAct=EBI-81752, EBI-1053685;
CC P60953; Q9NPB6: PARD6A; NbExp=7; IntAct=EBI-81752, EBI-81876;
CC P60953; Q9BYG5: PARD6B; NbExp=18; IntAct=EBI-81752, EBI-295391;
CC P60953; Q9BYG4: PARD6G; NbExp=5; IntAct=EBI-81752, EBI-295417;
CC P60953; P41743: PRKCI; NbExp=5; IntAct=EBI-81752, EBI-286199;
CC P60953; Q92963: RIT1; NbExp=6; IntAct=EBI-81752, EBI-365845;
CC P60953; P42768: WAS; NbExp=12; IntAct=EBI-81752, EBI-346375;
CC P60953; O00401: WASL; NbExp=3; IntAct=EBI-81752, EBI-957615;
CC P60953; Q9VEX9: Bin1; Xeno; NbExp=2; IntAct=EBI-81752, EBI-129424;
CC P60953; Q61036: Pak3; Xeno; NbExp=3; IntAct=EBI-81752, EBI-457317;
CC P60953; Q9JK83: Pard6b; Xeno; NbExp=6; IntAct=EBI-81752, EBI-81861;
CC P60953; A0A0H3NA16: sopB; Xeno; NbExp=2; IntAct=EBI-81752, EBI-10726187;
CC P60953; O30916: sopB; Xeno; NbExp=5; IntAct=EBI-81752, EBI-11167349;
CC P60953; O52623: sopE; Xeno; NbExp=2; IntAct=EBI-81752, EBI-602254;
CC P60953; O08816: Wasl; Xeno; NbExp=2; IntAct=EBI-81752, EBI-6142604;
CC P60953-1; Q15811: ITSN1; NbExp=2; IntAct=EBI-3625591, EBI-602041;
CC P60953-2; Q07960: ARHGAP1; NbExp=3; IntAct=EBI-287394, EBI-602762;
CC P60953-2; Q14155: ARHGEF7; NbExp=3; IntAct=EBI-287394, EBI-717515;
CC P60953-2; Q9UQB8: BAIAP2; NbExp=2; IntAct=EBI-287394, EBI-525456;
CC P60953-2; Q9UQB8-4: BAIAP2; NbExp=5; IntAct=EBI-287394, EBI-6174091;
CC P60953-2; O75914: PAK3; NbExp=2; IntAct=EBI-287394, EBI-3389553;
CC P60953-2; Q8TCU6: PREX1; NbExp=2; IntAct=EBI-287394, EBI-1046542;
CC P60953-2; Q07912: TNK2; NbExp=2; IntAct=EBI-287394, EBI-603457;
CC P60953-2; Q9R8E4: map; Xeno; NbExp=5; IntAct=EBI-287394, EBI-15794593;
CC P60953-2; Q64096: Mcf2l; Xeno; NbExp=4; IntAct=EBI-287394, EBI-602123;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:15642749}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:15642749}. Midbody {ECO:0000269|PubMed:15642749}.
CC Cell projection, dendrite {ECO:0000250|UniProtKB:P60766}.
CC Note=Localizes to spindle during prometaphase cells. Moves to the
CC central spindle as cells progressed through anaphase to telophase
CC (PubMed:15642749). Localizes at the end of cytokinesis in the
CC intercellular bridge formed between two daughter cells
CC (PubMed:15642749). Its localization is regulated by the activities of
CC guanine nucleotide exchange factor ECT2 and GTPase activating protein
CC RACGAP1 (PubMed:15642749). Colocalizes with NEK6 in the centrosome
CC (PubMed:20873783). In its active GTP-bound form localizes to the
CC leading edge membrane of migrating dendritic cells (By similarity).
CC {ECO:0000250|UniProtKB:P60766, ECO:0000269|PubMed:15642749,
CC ECO:0000269|PubMed:20873783}.
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: (Microbial infection) AMPylation at Tyr-32 and Thr-35 are mediated
CC by bacterial enzymes in case of infection by H.somnus and
CC V.parahaemolyticus, respectively. AMPylation occurs in the effector
CC region and leads to inactivation of the GTPase activity by preventing
CC the interaction with downstream effectors, thereby inhibiting actin
CC assembly in infected cells. It is unclear whether some human enzyme
CC mediates AMPylation; FICD has such ability in vitro but additional
CC experiments remain to be done to confirm results in vivo.
CC {ECO:0000269|PubMed:19039103, ECO:0000269|PubMed:19362538,
CC ECO:0000269|PubMed:20622875}.
CC -!- PTM: Phosphorylated by SRC in an EGF-dependent manner, this stimulates
CC the binding of the Rho-GDP dissociation inhibitor RhoGDI.
CC {ECO:0000269|PubMed:14506284}.
CC -!- PTM: (Microbial infection) Glycosylated at Tyr-32 by Photorhabdus
CC asymbiotica toxin PAU_02230. Mono-O-GlcNAcylation by PAU_02230 inhibits
CC downstream signaling by an impaired interaction with diverse regulator
CC and effector proteins of CDC42 and leads to actin disassembly.
CC {ECO:0000269|PubMed:24141704}.
CC -!- PTM: (Microbial infection) Glucosylated at Thr-35 by C.difficile toxins
CC TcdA and TcdB in the colonic epithelium (PubMed:7777059,
CC PubMed:7775453, PubMed:24905543). Monoglucosylation completely prevents
CC the recognition of the downstream effector, blocking the GTPases in
CC their inactive form, leading to actin cytoskeleton disruption and cell
CC death, resulting in the loss of colonic epithelial barrier function
CC (PubMed:7777059, PubMed:7775453). {ECO:0000269|PubMed:24905543,
CC ECO:0000269|PubMed:7775453, ECO:0000269|PubMed:7777059}.
CC -!- PTM: (Microbial infection) Glycosylated (O-GlcNAcylated) at Thr-35 by
CC C.novyi toxin TcdA (PubMed:8810274). O-GlcNAcylation completely
CC prevents the recognition of the downstream effector, blocking the
CC GTPases in their inactive form, leading to actin cytoskeleton
CC disruption (PubMed:8810274). {ECO:0000269|PubMed:8810274}.
CC -!- DISEASE: Takenouchi-Kosaki syndrome (TKS) [MIM:616737]: An autosomal
CC dominant syndrome characterized by macrothrombocytopenia, lymphedema,
CC intellectual disability, developmental delay, and distinctive facial
CC features. {ECO:0000269|PubMed:26386261, ECO:0000269|PubMed:26708094}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family. CDC42
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CDC42ID40012ch1p36.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdc42/";
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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; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002711; AAH02711.1; -; mRNA.
DR EMBL; BC003682; AAH03682.1; -; mRNA.
DR EMBL; BC018266; AAH18266.1; -; mRNA.
DR CCDS; CCDS221.1; -.
DR CCDS; CCDS222.1; -. [P60953-1]
DR PIR; A36382; A36382.
DR PIR; A39265; A39265.
DR RefSeq; NP_001034891.1; NM_001039802.1. [P60953-2]
DR RefSeq; NP_001782.1; NM_001791.3. [P60953-2]
DR RefSeq; NP_426359.1; NM_044472.2. [P60953-1]
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=1-190.
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=1-188.
DR PDB; 1KZ7; X-ray; 2.40 A; B/D=1-188.
DR PDB; 1KZG; X-ray; 2.60 A; B/D=1-188.
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=1-188.
DR PDB; 4DID; X-ray; 2.35 A; A=1-183.
DR PDB; 4ITR; X-ray; 2.30 A; C/D=1-191.
DR PDB; 4JS0; X-ray; 1.90 A; A=1-178.
DR PDB; 4YC7; X-ray; 2.50 A; A=1-179.
DR PDB; 4YDH; X-ray; 3.80 A; B/D=1-179.
DR PDB; 5CJP; X-ray; 2.60 A; A/B/C/D=1-177.
DR PDB; 5FI1; X-ray; 3.20 A; B=1-191.
DR PDB; 5HZK; X-ray; 3.30 A; A/C=1-181.
DR PDB; 5UPK; X-ray; 2.40 A; C=1-177.
DR PDB; 5UPL; X-ray; 3.00 A; B=1-177.
DR PDB; 6AJ4; X-ray; 3.26 A; B/D/F/H=1-188.
DR PDB; 6AJL; X-ray; 3.23 A; B/D/F/H=1-188.
DR PDB; 6SIU; X-ray; 2.49 A; C/D=1-191.
DR PDB; 6SUP; X-ray; 2.00 A; A=167-179.
DR PDB; 6TKY; X-ray; 2.55 A; C/D=1-188.
DR PDB; 6TKZ; X-ray; 2.64 A; C/D=1-188.
DR PDB; 7S0Y; X-ray; 2.79 A; B=4-179.
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 PDBsum; 4JS0; -.
DR PDBsum; 4YC7; -.
DR PDBsum; 4YDH; -.
DR PDBsum; 5CJP; -.
DR PDBsum; 5FI1; -.
DR PDBsum; 5HZK; -.
DR PDBsum; 5UPK; -.
DR PDBsum; 5UPL; -.
DR PDBsum; 6AJ4; -.
DR PDBsum; 6AJL; -.
DR PDBsum; 6SIU; -.
DR PDBsum; 6SUP; -.
DR PDBsum; 6TKY; -.
DR PDBsum; 6TKZ; -.
DR PDBsum; 7S0Y; -.
DR AlphaFoldDB; P60953; -.
DR BMRB; P60953; -.
DR SMR; P60953; -.
DR BioGRID; 107433; 1261.
DR CORUM; P60953; -.
DR DIP; DIP-31097N; -.
DR ELM; P60953; -.
DR IntAct; P60953; 266.
DR MINT; P60953; -.
DR STRING; 9606.ENSP00000383118; -.
DR BindingDB; P60953; -.
DR ChEMBL; CHEMBL6088; -.
DR DrugBank; DB02623; Aminophosphonic acid-guanylate ester.
DR DrugBank; DB04315; Guanosine-5'-Diphosphate.
DR MoonDB; P60953; Predicted.
DR GlyGen; P60953; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P60953; -.
DR PhosphoSitePlus; P60953; -.
DR SwissPalm; P60953; -.
DR BioMuta; CDC42; -.
DR DMDM; 322510015; -.
DR CPTAC; CPTAC-1601; -.
DR EPD; P60953; -.
DR jPOST; P60953; -.
DR MassIVE; P60953; -.
DR MaxQB; P60953; -.
DR PaxDb; P60953; -.
DR PeptideAtlas; P60953; -.
DR PRIDE; P60953; -.
DR ProteomicsDB; 57238; -.
DR ProteomicsDB; 57239; -. [P60953-1]
DR TopDownProteomics; P60953-2; -. [P60953-2]
DR Antibodypedia; 3818; 531 antibodies from 42 providers.
DR DNASU; 998; -.
DR Ensembl; ENST00000315554.13; ENSP00000314458.8; ENSG00000070831.17. [P60953-1]
DR Ensembl; ENST00000344548.7; ENSP00000341072.3; ENSG00000070831.17. [P60953-2]
DR Ensembl; ENST00000400259.5; ENSP00000383118.1; ENSG00000070831.17. [P60953-2]
DR Ensembl; ENST00000648594.1; ENSP00000497733.1; ENSG00000070831.17. [P60953-2]
DR Ensembl; ENST00000656825.1; ENSP00000499457.1; ENSG00000070831.17. [P60953-2]
DR Ensembl; ENST00000662562.1; ENSP00000499612.1; ENSG00000070831.17. [P60953-2]
DR GeneID; 998; -.
DR KEGG; hsa:998; -.
DR MANE-Select; ENST00000656825.1; ENSP00000499457.1; NM_001791.4; NP_001782.1.
DR UCSC; uc001bfp.4; human.
DR CTD; 998; -.
DR DisGeNET; 998; -.
DR GeneCards; CDC42; -.
DR HGNC; HGNC:1736; CDC42.
DR HPA; ENSG00000070831; Low tissue specificity.
DR MalaCards; CDC42; -.
DR MIM; 116952; gene.
DR MIM; 616737; phenotype.
DR neXtProt; NX_P60953; -.
DR OpenTargets; ENSG00000070831; -.
DR Orphanet; 487796; Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome.
DR Orphanet; 619363; Neonatal-onset severe multisystemic autoinflammatory disease with increased IL18.
DR PharmGKB; PA26266; -.
DR VEuPathDB; HostDB:ENSG00000070831; -.
DR eggNOG; KOG0393; Eukaryota.
DR GeneTree; ENSGT00940000153675; -.
DR HOGENOM; CLU_041217_21_3_1; -.
DR InParanoid; P60953; -.
DR OMA; ITHHQQK; -.
DR PhylomeDB; P60953; -.
DR TreeFam; TF101109; -.
DR BRENDA; 3.6.5.2; 2681.
DR PathwayCommons; P60953; -.
DR Reactome; R-HSA-114604; GPVI-mediated activation cascade.
DR Reactome; R-HSA-182971; EGFR downregulation.
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-HSA-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling.
DR Reactome; R-HSA-418885; DCC mediated attractive signaling.
DR Reactome; R-HSA-428543; Inactivation of CDC42 and RAC1.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-HSA-525793; Myogenesis.
DR Reactome; R-HSA-5625970; RHO GTPases activate KTN1.
DR Reactome; R-HSA-5626467; RHO GTPases activate IQGAPs.
DR Reactome; R-HSA-5627123; RHO GTPases activate PAKs.
DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-HSA-8950505; Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation.
DR Reactome; R-HSA-8964616; G beta:gamma signalling through CDC42.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-9013424; RHOV GTPase cycle.
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; P60953; -.
DR SIGNOR; P60953; -.
DR BioGRID-ORCS; 998; 652 hits in 1023 CRISPR screens.
DR ChiTaRS; CDC42; human.
DR EvolutionaryTrace; P60953; -.
DR GeneWiki; CDC42; -.
DR GenomeRNAi; 998; -.
DR Pharos; P60953; Tchem.
DR PRO; PR:P60953; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P60953; protein.
DR Bgee; ENSG00000070831; Expressed in cortical plate and 202 other tissues.
DR ExpressionAtlas; P60953; baseline and differential.
DR Genevisible; P60953; HS.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; IDA:SynGO.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:BHF-UCL.
DR GO; GO:0017119; C:Golgi transport complex; IMP:CAFA.
DR GO; GO:0031256; C:leading edge membrane; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
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:0045335; C:phagocytic vesicle; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0051233; C:spindle midzone; IDA:UniProtKB.
DR GO; GO:0000322; C:storage vacuole; IEA:Ensembl.
DR GO; GO:0034191; F:apolipoprotein A-I receptor binding; IPI:BHF-UCL.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0032427; F:GBD domain binding; IPI:CAFA.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0030742; F:GTP-dependent protein binding; IEA:Ensembl.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019901; F:protein kinase binding; IDA:BHF-UCL.
DR GO; GO:0031996; F:thioesterase binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:AgBase.
DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IMP:UniProtKB.
DR GO; GO:0034332; P:adherens junction organization; IEA:Ensembl.
DR GO; GO:0003161; P:cardiac conduction system development; IEA:Ensembl.
DR GO; GO:0003253; P:cardiac neural crest cell migration involved in outflow tract morphogenesis; IEA:Ensembl.
DR GO; GO:0032488; P:Cdc42 protein signal transduction; IBA:GO_Central.
DR GO; GO:0034329; P:cell junction assembly; IMP:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEA:Ensembl.
DR GO; GO:0036336; P:dendritic cell migration; IEA:Ensembl.
DR GO; GO:0060997; P:dendritic spine morphogenesis; ISS:UniProtKB.
DR GO; GO:0035050; P:embryonic heart tube development; IEA:Ensembl.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0086101; P:endothelin receptor signaling pathway involved in heart process; IEA:Ensembl.
DR GO; GO:0045198; P:establishment of epithelial cell apical/basal polarity; IMP:UniProtKB.
DR GO; GO:0051683; P:establishment of Golgi localization; ISS:BHF-UCL.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IBA:GO_Central.
DR GO; GO:0046847; P:filopodium assembly; IEA:Ensembl.
DR GO; GO:0007030; P:Golgi organization; ISS:BHF-UCL.
DR GO; GO:0060047; P:heart contraction; IEA:Ensembl.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IMP:BHF-UCL.
DR GO; GO:0030225; P:macrophage differentiation; TAS:UniProtKB.
DR GO; GO:0099563; P:modification of synaptic structure; IBA:GO_Central.
DR GO; GO:0044788; P:modulation by host of viral process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IPI:UniProtKB.
DR GO; GO:0048664; P:neuron fate determination; IEA:Ensembl.
DR GO; GO:0038189; P:neuropilin signaling pathway; IMP:BHF-UCL.
DR GO; GO:0007097; P:nuclear migration; IEA:Ensembl.
DR GO; GO:0072384; P:organelle transport along microtubule; ISS:BHF-UCL.
DR GO; GO:0006911; P:phagocytosis, engulfment; IMP:UniProtKB.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; IMP:BHF-UCL.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:AgBase.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB.
DR GO; GO:0060501; P:positive regulation of epithelial cell proliferation involved in lung morphogenesis; IEA:Ensembl.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; IMP:BHF-UCL.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IMP:CAFA.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IEA:Ensembl.
DR GO; GO:0048549; P:positive regulation of pinocytosis; ISS:UniProtKB.
DR GO; GO:0031274; P:positive regulation of pseudopodium assembly; IDA:UniProtKB.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IMP:BHF-UCL.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IDA:UniProtKB.
DR GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; 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:0010591; P:regulation of lamellipodium assembly; IGI:CAFA.
DR GO; GO:0007088; P:regulation of mitotic nuclear division; IEA:Ensembl.
DR GO; GO:0043393; P:regulation of protein binding; IEA:Ensembl.
DR GO; GO:0051492; P:regulation of stress fiber assembly; IGI:CAFA.
DR GO; GO:0021762; P:substantia nigra development; HEP:UniProtKB.
DR GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; NAS:ParkinsonsUK-UCL.
DR CDD; cd01874; Cdc42; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR IDEAL; IID00308; -.
DR InterPro; IPR037874; Cdc42.
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 PANTHER; PTHR24072; PTHR24072; 1.
DR Pfam; PF00071; Ras; 1.
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; Cell projection;
KW Cytoplasm; Cytoskeleton; Differentiation; Direct protein sequencing;
KW Disease variant; Glycoprotein; GTP-binding; Hydrolase;
KW Intellectual disability; Lipoprotein; Membrane; Methylation; Neurogenesis;
KW Nucleotide-binding; Phosphoprotein; Prenylation; Reference proteome.
FT CHAIN 1..188
FT /note="Cell division control protein 42 homolog"
FT /id="PRO_0000030425"
FT PROPEP 189..191
FT /note="Removed in mature form"
FT /id="PRO_0000030426"
FT MOTIF 32..40
FT /note="Effector region"
FT /evidence="ECO:0000255"
FT BINDING 10..17
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 57..61
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 115..118
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT MOD_RES 32
FT /note="(Microbial infection) O-AMP-tyrosine; by Haemophilus
FT IbpA; alternate"
FT /evidence="ECO:0000269|PubMed:19362538,
FT ECO:0000269|PubMed:20622875"
FT MOD_RES 35
FT /note="(Microbial infection) O-AMP-threonine; by Vibrio
FT VopS"
FT /evidence="ECO:0000269|PubMed:19039103"
FT MOD_RES 64
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:14506284"
FT MOD_RES 188
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000269|PubMed:10676816,
FT ECO:0007744|PDB:1DOA"
FT LIPID 188
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000269|PubMed:10676816,
FT ECO:0007744|PDB:1DOA"
FT CARBOHYD 32
FT /note="(Microbial infection) O-linked (GlcNAc) tyrosine; by
FT Photorhabdus PAU_02230; alternate"
FT /evidence="ECO:0000269|PubMed:24141704"
FT CARBOHYD 35
FT /note="(Microbial infection) O-alpha-linked (GlcNAc)
FT threonine; by C.novyi toxin TcdA; alternate"
FT /evidence="ECO:0000269|PubMed:8810274"
FT CARBOHYD 35
FT /note="(Microbial infection) O-linked (Glc) threonine; by
FT C.difficile toxins TcdA and TcdB; alternate"
FT /evidence="ECO:0000269|PubMed:24905543,
FT ECO:0000269|PubMed:7775453, ECO:0000269|PubMed:7777059"
FT VAR_SEQ 163
FT /note="K -> R (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:2122236, ECO:0000303|Ref.3,
FT ECO:0000303|Ref.4"
FT /id="VSP_040583"
FT VAR_SEQ 182..191
FT /note="PKKSRRCVLL -> TQPKRKCCIF (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:2122236, ECO:0000303|Ref.3,
FT ECO:0000303|Ref.4"
FT /id="VSP_040584"
FT VARIANT 64
FT /note="Y -> C (in TKS; dbSNP:rs864309721)"
FT /evidence="ECO:0000269|PubMed:26386261,
FT ECO:0000269|PubMed:26708094"
FT /id="VAR_076337"
FT MUTAGEN 12
FT /note="G->V: Constitutively active. Interacts with PARD6
FT proteins. Does not inhibit filopodia formation. No effect
FT on NR3C2 transcriptional activity."
FT /evidence="ECO:0000269|PubMed:10954424,
FT ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:19029984"
FT MUTAGEN 17
FT /note="T->N: Constitutively inactive. Does not interact
FT with PARD6 proteins. Inhibits filopodia formation. No
FT effect on NR3C2 transcriptional activity."
FT /evidence="ECO:0000269|PubMed:11260256,
FT ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:19029984"
FT MUTAGEN 32
FT /note="Y->F: Abolishes AMPylation by Haemophilus IbpA."
FT /evidence="ECO:0000269|PubMed:19362538"
FT MUTAGEN 61
FT /note="Q->L: Constitutively active. Interacts with PARD6
FT proteins."
FT /evidence="ECO:0000269|PubMed:11260256"
FT STRAND 2..11
FT /evidence="ECO:0007829|PDB:2NGR"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:6TKY"
FT HELIX 16..25
FT /evidence="ECO:0007829|PDB:2NGR"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:3VHL"
FT STRAND 36..46
FT /evidence="ECO:0007829|PDB:2NGR"
FT STRAND 49..58
FT /evidence="ECO:0007829|PDB:2NGR"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:2NGR"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:2NGR"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:2NGR"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:3QBV"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:2NGR"
FT HELIX 87..95
FT /evidence="ECO:0007829|PDB:2NGR"
FT HELIX 97..104
FT /evidence="ECO:0007829|PDB:2NGR"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:2WMN"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:2NGR"
FT HELIX 117..121
FT /evidence="ECO:0007829|PDB:2NGR"
FT HELIX 123..130
FT /evidence="ECO:0007829|PDB:2NGR"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:2NGR"
FT HELIX 139..148
FT /evidence="ECO:0007829|PDB:2NGR"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:2NGR"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:2NGR"
FT TURN 162..164
FT /evidence="ECO:0007829|PDB:2KB0"
FT HELIX 165..176
FT /evidence="ECO:0007829|PDB:2NGR"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:1NF3"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:1NF3"
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
