CDC42_CAEEL
ID CDC42_CAEEL Reviewed; 191 AA.
AC Q05062; P91792;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 31-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Cell division control protein 42 homolog;
DE AltName: Full=CDC42Ce;
DE Flags: Precursor;
GN Name=cdc-42 {ECO:0000312|WormBase:R07G3.1};
GN ORFNames=R07G3.1 {ECO:0000312|WormBase:R07G3.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=Bristol N2;
RX PubMed=8514766; DOI=10.1016/s0021-9258(19)38649-1;
RA Chen W., Lim H., Lim L.;
RT "The CDC42 homologue from Caenorhabditis elegans. Complementation of yeast
RT mutation.";
RL J. Biol. Chem. 268:13280-13285(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8722777; DOI=10.1093/genetics/143.1.225;
RA Run J.-Q., Steven R., Hung M.-S., van Weeghel R., Culotti J.G., Way J.C.;
RT "Suppressors of the unc-73 gene of Caenorhabditis elegans.";
RL Genetics 143:225-236(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [4]
RP FUNCTION.
RC STRAIN=Bristol N2; TISSUE=Embryo;
RX PubMed=11412996; DOI=10.1016/s0960-9822(01)00141-5;
RA Kay A.J., Hunter C.P.;
RT "CDC-42 regulates PAR protein localization and function to control cellular
RT and embryonic polarity in C. elegans.";
RL Curr. Biol. 11:474-481(2001).
RN [5]
RP FUNCTION, INTERACTION WITH PAK-1, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=8824291; DOI=10.1074/jbc.271.42.26362;
RA Chen W., Chen S., Yap S.F., Lim L.;
RT "The Caenorhabditis elegans p21-activated kinase (CePAK) colocalizes with
RT CeRac1 and CDC42Ce at hypodermal cell boundaries during embryo
RT elongation.";
RL J. Biol. Chem. 271:26362-26368(1996).
RN [6]
RP FUNCTION, AND INTERACTION WITH PAR-6.
RC STRAIN=Bristol N2; TISSUE=Embryo;
RX PubMed=11412997; DOI=10.1016/s0960-9822(01)00142-7;
RA Gotta M., Abraham M.C., Ahringer J.;
RT "CDC-42 controls early cell polarity and spindle orientation in C.
RT elegans.";
RL Curr. Biol. 11:482-488(2001).
RN [7]
RP INTERACTION WITH UNC-89.
RX PubMed=18801371; DOI=10.1016/j.jmb.2008.08.083;
RA Qadota H., Blangy A., Xiong G., Benian G.M.;
RT "The DH-PH region of the giant protein UNC-89 activates RHO-1 GTPase in
RT Caenorhabditis elegans body wall muscle.";
RL J. Mol. Biol. 383:747-752(2008).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19023419; DOI=10.1371/journal.pgen.1000269;
RA Lucanic M., Cheng H.J.;
RT "A RAC/CDC-42-independent GIT/PIX/PAK signaling pathway mediates cell
RT migration in C. elegans.";
RL PLoS Genet. 4:E1000269-E1000269(2008).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF GLN-61.
RX PubMed=19797046; DOI=10.1534/genetics.109.106880;
RA Locke C.J., Kautu B.B., Berry K.P., Lee S.K., Caldwell K.A., Caldwell G.A.;
RT "Pharmacogenetic analysis reveals a post-developmental role for Rac GTPases
RT in Caenorhabditis elegans GABAergic neurotransmission.";
RL Genetics 183:1357-1372(2009).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=21408209; DOI=10.1371/journal.pgen.1002010;
RA Nelson M.D., Zhou E., Kiontke K., Fradin H., Maldonado G., Martin D.,
RA Shah K., Fitch D.H.;
RT "A bow-tie genetic architecture for morphogenesis suggested by a genome-
RT wide RNAi screen in Caenorhabditis elegans.";
RL PLoS Genet. 7:E1002010-E1002010(2011).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=25743393; DOI=10.1038/ncomms7449;
RA Lant B., Yu B., Goudreault M., Holmyard D., Knight J.D., Xu P., Zhao L.,
RA Chin K., Wallace E., Zhen M., Gingras A.C., Derry W.B.;
RT "CCM-3/STRIPAK promotes seamless tube extension through endocytic
RT recycling.";
RL Nat. Commun. 6:6449-6449(2015).
RN [13]
RP FUNCTION, INTERACTION WITH TOCA-1 AND TOCA-2, SUBCELLULAR LOCATION,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-12.
RX PubMed=25775511; DOI=10.1073/pnas.1418651112;
RA Bai Z., Grant B.D.;
RT "A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic
RT recycling.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:E1443-E1452(2015).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=27506200; DOI=10.1186/s12915-016-0286-x;
RA Waaijers S., Munoz J., Berends C., Ramalho J.J., Goerdayal S.S., Low T.Y.,
RA Zoumaro-Djayoon A.D., Hoffmann M., Koorman T., Tas R.P., Harterink M.,
RA Seelk S., Kerver J., Hoogenraad C.C., Bossinger O., Tursun B.,
RA van den Heuvel S., Heck A.J., Boxem M.;
RT "A tissue-specific protein purification approach in Caenorhabditis elegans
RT identifies novel interaction partners of DLG-1/Discs large.";
RL BMC Biol. 14:66-66(2016).
RN [15]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLN-61.
RX PubMed=28846083; DOI=10.1038/nn.4630;
RA Rapti G., Li C., Shan A., Lu Y., Shaham S.;
RT "Glia initiate brain assembly through noncanonical Chimaerin-Furin axon
RT guidance in C. elegans.";
RL Nat. Neurosci. 20:1350-1360(2017).
CC -!- FUNCTION: Plays an essential role in spindle orientation and organizing
CC cellular and embryonic polarity by controlling the localization and
CC activity of PAR (partitioning-defective) proteins. Required for
CC maintaining the asymmetric cortical localization of the anterior
CC complex proteins par-3 and par-6, the posterior cortical protein par-2,
CC and pkc-3 (PubMed:11412996, PubMed:11412997). Involved in hypodermal
CC cell fusion, together with pak-1 and ced-10, leading to embryonic body
CC elongation, which involves dramatic cytoskeletal reorganization
CC (PubMed:8824291). During gonad morphogenesis, plays a role in distal
CC tip cell (DTC)-mediated guidance of gonad elongation, probably by
CC activating max-2 (PubMed:19797046, PubMed:19023419). May play a role in
CC controlling canal length and in maintaining Golgi and ER stability
CC during excretory canal elongation, probably downstream of ccm-3, which
CC may regulate its activity and expression levels (PubMed:25743393). May
CC play a role in yolk protein clatherin-mediated endocytosis by oocytes
CC during oogenesis (PubMed:19798448). Involved in toca-1 and toca-2-
CC mediated protein trafficking controlling the recycling of endocytic
CC cargo protein mig-14 to the Golgi apparatus (PubMed:25775511). Plays a
CC role in male tail tip morphogenesis (PubMed:21408209). Together with
CC kpc-1 and chin-1, plays a role in guiding axons from neurons, including
CC AIY interneurons, into the nerve ring (PubMed:28846083).
CC {ECO:0000269|PubMed:11412996, ECO:0000269|PubMed:11412997,
CC ECO:0000269|PubMed:19023419, ECO:0000269|PubMed:19797046,
CC ECO:0000269|PubMed:19798448, ECO:0000269|PubMed:21408209,
CC ECO:0000269|PubMed:25743393, ECO:0000269|PubMed:25775511,
CC ECO:0000269|PubMed:28846083, ECO:0000269|PubMed:8824291}.
CC -!- SUBUNIT: The GTP-bound, but not the GDP-bound, form binds to the p21-
CC activated kinase (pak-1) (PubMed:8824291). Interaction with par-6
CC required for activation of the par-3/par-6/pkc-3 complex
CC (PubMed:11412997). Interacts with toca-1 and toca-2 (PubMed:25775511).
CC May interact with unc-89 (via DH and PH domains); the interaction does
CC not stimulate GTPase activity in vitro (PubMed:18801371).
CC {ECO:0000269|PubMed:11412997, ECO:0000269|PubMed:18801371,
CC ECO:0000269|PubMed:25775511, ECO:0000269|PubMed:8824291}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27506200,
CC ECO:0000269|PubMed:8824291}; Lipid-anchor {ECO:0000305}; Cytoplasmic
CC side {ECO:0000269|PubMed:21408209, ECO:0000269|PubMed:8824291}.
CC Recycling endosome {ECO:0000269|PubMed:25775511}. Cytoplasm
CC {ECO:0000269|PubMed:21408209}. Note=Co-localizes with ced-10/rac-1 and
CC pak-1 at hypodermal cell boundaries during embryo elongation
CC (PubMed:8824291). Localizes in punctate cytoplasmic structures along
CC the length of excretory canals (PubMed:25743393). Co-localizes with
CC rme-1 and toca-1 on recycling endosomes (PubMed:25775511). Diffusely
CC localizes in the cytoplasm of tail tip cells, but then localizes to the
CC apical surfaces of the tail tip cells before male tail tip retraction
CC during the L4 larval stage (PubMed:21408209). During male tail tip
CC retraction localizes to the cytoplasm (PubMed:21408209).
CC {ECO:0000269|PubMed:21408209, ECO:0000269|PubMed:25743393,
CC ECO:0000269|PubMed:25775511, ECO:0000269|PubMed:8824291}.
CC -!- TISSUE SPECIFICITY: Expressed in the intestine and seam cells.
CC {ECO:0000269|PubMed:27506200}.
CC -!- DEVELOPMENTAL STAGE: Highest levels at the embryonic stage, decreasing
CC progressively during development, except for an increase at the L3
CC stage (PubMed:8514766). Expressed in hypodermal cells during elongation
CC throughout the second phase of embryogenesis (PubMed:8824291).
CC {ECO:0000269|PubMed:8514766, ECO:0000269|PubMed:8824291}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown disrupts tail tip
CC morphogenesis resulting in retention of the pointed larval tail tip in
CC adult males (also known as the Lep phenotype) (PubMed:21408209). RNAi-
CC mediated knockdown in distal tip cells (DTC) causes additional turns
CC during their migration (PubMed:19023419). RNAi-mediated knockdown in
CC addition, causes a truncation of excretory canals associated with the
CC formation of cysts and a reduced distribution of Golgi and ER
CC components along the excretory canal length (PubMed:25743393). RNAi-
CC mediated knockdown results in defective endocytosis by oocytes
CC characterized by an accumulation of aggregated yolk protein in the
CC pseudocoelomatic space, and accumulation of endocytic cargo protein
CC mig-14 in late endosomes and expansion of recycling endosomes that
CC express toca-1 and toca-2 (PubMed:19798448, PubMed:25775511). RNAi-
CC mediated knockdown enhances the axon guidance defects in glia and
CC sublateral neurons of the kpc-1 gk mutant, in which non-commissural
CC interneurons AIY fail to extend dorsally and enter the nerve ring
CC (PubMed:28846083). {ECO:0000269|PubMed:19023419,
CC ECO:0000269|PubMed:19798448, ECO:0000269|PubMed:21408209,
CC ECO:0000269|PubMed:25743393, ECO:0000269|PubMed:25775511,
CC ECO:0000269|PubMed:28846083}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family. CDC42
CC subfamily. {ECO:0000305}.
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DR EMBL; L10078; AAA51433.1; -; mRNA.
DR EMBL; S82771; AAC05600.1; -; Genomic_DNA.
DR EMBL; BX284602; CCD70511.1; -; Genomic_DNA.
DR PIR; S68301; S68301.
DR RefSeq; NP_495598.1; NM_063197.7.
DR AlphaFoldDB; Q05062; -.
DR SMR; Q05062; -.
DR BioGRID; 39567; 36.
DR DIP; DIP-24428N; -.
DR IntAct; Q05062; 4.
DR STRING; 6239.R07G3.1; -.
DR EPD; Q05062; -.
DR PaxDb; Q05062; -.
DR PeptideAtlas; Q05062; -.
DR EnsemblMetazoa; R07G3.1.1; R07G3.1.1; WBGene00000390.
DR GeneID; 174233; -.
DR KEGG; cel:CELE_R07G3.1; -.
DR UCSC; R07G3.1; c. elegans.
DR CTD; 174233; -.
DR WormBase; R07G3.1; CE02020; WBGene00000390; cdc-42.
DR eggNOG; KOG0393; Eukaryota.
DR GeneTree; ENSGT00940000153675; -.
DR HOGENOM; CLU_041217_21_3_1; -.
DR InParanoid; Q05062; -.
DR OMA; ITHHQQK; -.
DR OrthoDB; 1091615at2759; -.
DR PhylomeDB; Q05062; -.
DR Reactome; R-CEL-114604; GPVI-mediated activation cascade.
DR Reactome; R-CEL-182971; EGFR downregulation.
DR Reactome; R-CEL-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-CEL-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-CEL-3928662; EPHB-mediated forward signaling.
DR Reactome; R-CEL-418885; DCC mediated attractive signaling.
DR Reactome; R-CEL-525793; Myogenesis.
DR Reactome; R-CEL-5626467; RHO GTPases activate IQGAPs.
DR Reactome; R-CEL-5627123; RHO GTPases activate PAKs.
DR Reactome; R-CEL-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-CEL-5663220; RHO GTPases Activate Formins.
DR Reactome; R-CEL-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-CEL-8964616; G beta:gamma signalling through CDC42.
DR Reactome; R-CEL-9013148; CDC42 GTPase cycle.
DR Reactome; R-CEL-9013149; RAC1 GTPase cycle.
DR Reactome; R-CEL-9013420; RHOU GTPase cycle.
DR Reactome; R-CEL-9013424; RHOV GTPase cycle.
DR Reactome; R-CEL-983231; Factors involved in megakaryocyte development and platelet production.
DR PRO; PR:Q05062; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00000390; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005938; C:cell cortex; IDA:WormBase.
DR GO; GO:0005813; C:centrosome; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005829; C:cytosol; IDA:WormBase.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:WormBase.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0055037; C:recycling endosome; IDA:WormBase.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0032488; P:Cdc42 protein signal transduction; IBA:GO_Central.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0060562; P:epithelial tube morphogenesis; IMP:UniProtKB.
DR GO; GO:0040001; P:establishment of mitotic spindle localization; IGI:UniProtKB.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:WormBase.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IMP:WormBase.
DR GO; GO:2000370; P:positive regulation of clathrin-dependent endocytosis; IMP:UniProtKB.
DR GO; GO:0110039; P:positive regulation of nematode male tail tip morphogenesis; IMP:UniProtKB.
DR GO; GO:0032970; P:regulation of actin filament-based process; IMP:WormBase.
DR GO; GO:1903358; P:regulation of Golgi organization; IMP:UniProtKB.
DR CDD; cd01874; Cdc42; 1.
DR Gene3D; 3.40.50.300; -; 1.
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 Cell cycle; Cell division; Cell membrane; Cytoplasm; Endosome; GTP-binding;
KW Lipoprotein; Membrane; Methylation; Nucleotide-binding; Prenylation;
KW Reference proteome.
FT CHAIN 1..188
FT /note="Cell division control protein 42 homolog"
FT /id="PRO_0000198959"
FT PROPEP 189..191
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281289"
FT MOTIF 32..40
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 10..17
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
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 /evidence="ECO:0000250"
FT MOD_RES 188
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 188
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT MUTAGEN 12
FT /note="G->V: In a cwn-1 mutant background results in ALM
FT polarity defects."
FT /evidence="ECO:0000269|PubMed:25775511"
FT MUTAGEN 61
FT /note="Q->L: May lock enzyme in its GTP-bound active state.
FT Defect in distal tip cell (DTC) migration. Partially
FT rescues the axon guidance defects of AIY interneurons in
FT kpc-1 (gk8) and chin-1 (ns399) double mutants."
FT /evidence="ECO:0000269|PubMed:19797046,
FT ECO:0000269|PubMed:28846083"
FT CONFLICT 1..4
FT /note="MQTI -> M (in Ref. 1; AAA51433)"
FT /evidence="ECO:0000305"
FT CONFLICT 44
FT /note="V -> A (in Ref. 2; AAC05600)"
FT /evidence="ECO:0000305"
FT CONFLICT 140
FT /note="D -> Y (in Ref. 2; AAC05600)"
FT /evidence="ECO:0000305"
FT CONFLICT 162..164
FT /note="QKG -> EKE (in Ref. 2; AAC05600)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 191 AA; 21165 MW; 38B7C025CC0FCB70 CRC64;
MQTIKCVVVG DGAVGKTCLL ISYTTNKFPS EYVPTVFDNY AVTVMIGGEP YTLGLFDTAG
QEDYDRLRPL SYPQTDVFLV CFSVVAPASF ENVREKWVPE ISHHCSKTPF LLVGTQVDLR
DDPGMLEKLA KNKQKPVSTD VGEKLAKELK AVKYVECSAL TQKGLKNVFD EAILAALDPP
QQEKKKKCNI L
