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Protein

Cell division control protein 42 homolog

Gene

CDC42

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration. Required for DOCK10-mediated spine formation in Purkinje cells and hippocampal neurons. Facilitates filopodia formation upon DOCK11-activation (By similarity).By similarity3 Publications

Enzyme regulationi

Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 17GTP8
Nucleotide bindingi57 – 61GTPBy similarity5
Nucleotide bindingi115 – 118GTP4

GO - Molecular functioni

  • apolipoprotein A-I receptor binding Source: BHF-UCL
  • GBD domain binding Source: CAFA
  • GTPase activity Source: UniProtKB
  • GTP binding Source: UniProtKB
  • GTP-dependent protein binding Source: Ensembl
  • identical protein binding Source: IntAct
  • mitogen-activated protein kinase kinase kinase binding Source: Ensembl
  • protein kinase binding Source: BHF-UCL
  • Rho GDP-dissociation inhibitor binding Source: Ensembl
  • thioesterase binding Source: UniProtKB
  • ubiquitin protein ligase activity Source: AgBase

GO - Biological processi

Keywordsi

Biological processDifferentiation, Neurogenesis
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-114604. GPVI-mediated activation cascade.
R-HSA-182971. EGFR downregulation.
R-HSA-194840. Rho GTPase cycle.
R-HSA-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-HSA-375170. CDO in myogenesis.
R-HSA-389359. CD28 dependent Vav1 pathway.
R-HSA-3928662. EPHB-mediated forward signaling.
R-HSA-416482. G alpha (12/13) signalling events.
R-HSA-416572. Sema4D induced cell migration and growth-cone collapse.
R-HSA-418885. DCC mediated attractive signaling.
R-HSA-428543. Inactivation of Cdc42 and Rac.
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
R-HSA-5625970. RHO GTPases activate KTN1.
R-HSA-5626467. RHO GTPases activate IQGAPs.
R-HSA-5627123. RHO GTPases activate PAKs.
R-HSA-5663213. RHO GTPases Activate WASPs and WAVEs.
R-HSA-5663220. RHO GTPases Activate Formins.
R-HSA-5687128. MAPK6/MAPK4 signaling.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SignaLinkiP60953.
SIGNORiP60953.

Names & Taxonomyi

Protein namesi
Recommended name:
Cell division control protein 42 homolog
Alternative name(s):
G25K GTP-binding protein
Gene namesi
Name:CDC42
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:1736. CDC42.

Subcellular locationi

GO - Cellular componenti

  • apical part of cell Source: Ensembl
  • cell-cell junction Source: Ensembl
  • cytoplasm Source: UniProtKB
  • cytoplasmic ribonucleoprotein granule Source: ParkinsonsUK-UCL
  • cytosol Source: Reactome
  • dendritic spine Source: SynGO
  • endoplasmic reticulum membrane Source: Reactome
  • extracellular exosome Source: UniProtKB
  • filopodium Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • Golgi membrane Source: BHF-UCL
  • Golgi transport complex Source: CAFA
  • leading edge membrane Source: Ensembl
  • membrane Source: UniProtKB
  • microtubule organizing center Source: UniProtKB-SubCell
  • midbody Source: UniProtKB
  • mitotic spindle Source: UniProtKB
  • myelin sheath Source: Ensembl
  • neuronal cell body Source: BHF-UCL
  • neuron projection Source: BHF-UCL
  • plasma membrane Source: UniProtKB
  • secretory granule Source: Ensembl
  • spindle midzone Source: UniProtKB
  • storage vacuole Source: Ensembl

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Involvement in diseasei

Takenouchi-Kosaki syndrome (TKS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by macrothrombocytopenia, lymphedema, mental retardation, developmental delay, and distinctive facial features.
See also OMIM:616737
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07633764Y → C in TKS. 2 PublicationsCorresponds to variant dbSNP:rs864309721Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi12G → V: Constitutively active. Interacts with PARD6 proteins. Does not inhibit filopodia formation. No effect on NR3C2 transcriptional activity. 3 Publications1
Mutagenesisi17T → N: Constitutively inactive. Does not interact with PARD6 proteins. Inhibits filopodia formation. No effect on NR3C2 transcriptional activity. 3 Publications1
Mutagenesisi32Y → F: Abolishes AMPylation by Haemophilus IbpA. 1 Publication1
Mutagenesisi61Q → L: Constitutively active. Interacts with PARD6 proteins. 1 Publication1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi998.
MalaCardsiCDC42.
MIMi616737. phenotype.
OpenTargetsiENSG00000070831.
PharmGKBiPA26266.

Chemistry databases

ChEMBLiCHEMBL6088.
DrugBankiDB02623. Aminophosphonic Acid-Guanylate Ester.
DB04315. Guanosine-5'-Diphosphate.

Polymorphism and mutation databases

BioMutaiCDC42.
DMDMi322510015.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000304251 – 188Cell division control protein 42 homologAdd BLAST188
PropeptideiPRO_0000030426189 – 191Removed in mature form3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei32O-AMP-tyrosine; by Haemophilus IbpA; alternate2 Publications1
Glycosylationi32O-linked (GlcNAc) tyrosine; by Photorhabdus PAU_02230; alternate1 Publication1
Modified residuei35O-AMP-threonine; by Vibrio VopS1 Publication1
Modified residuei64Phosphotyrosine; by SRC1 Publication1
Modified residuei188Cysteine methyl esterCombined sources1 Publication1
Lipidationi188S-geranylgeranyl cysteineCombined sources1 Publication1

Post-translational modificationi

(Microbial infection) AMPylation at Tyr-32 and Thr-35 are mediated by bacterial enzymes in case of infection by H.somnus and V.parahaemolyticus, respectively. AMPylation occurs in the effector region and leads to inactivation of the GTPase activity by preventing the interaction with downstream effectors, thereby inhibiting actin assembly in infected cells. It is unclear whether some human enzyme mediates AMPylation; FICD has such ability in vitro but additional experiments remain to be done to confirm results in vivo.3 Publications
Phosphorylated by SRC in an EGF-dependent manner, this stimulates the binding of the Rho-GDP dissociation inhibitor RhoGDI.1 Publication
(Microbial infection) Glycosylated at Tyr-32 by Photorhabdus asymbiotica toxin PAU_02230. Mono-O-GlcNAcylation by PAU_02230 inhibits downstream signaling by an impaired interaction with diverse regulator and effector proteins of CDC42 and leads to actin disassembly.1 Publication

Keywords - PTMi

Glycoprotein, Lipoprotein, Methylation, Phosphoprotein, Prenylation

Proteomic databases

EPDiP60953.
PaxDbiP60953.
PeptideAtlasiP60953.
PRIDEiP60953.
TopDownProteomicsiP60953-2. [P60953-2]

PTM databases

iPTMnetiP60953.
PhosphoSitePlusiP60953.
SwissPalmiP60953.

Miscellaneous databases

PMAP-CutDBiP60953.

Expressioni

Gene expression databases

BgeeiENSG00000070831.
CleanExiHS_CDC42.
ExpressionAtlasiP60953. baseline and differential.
GenevisibleiP60953. HS.

Organism-specific databases

HPAiCAB004360.

Interactioni

Subunit structurei

The GTP-bound form interacts with CCPG1 (By similarity). Interacts with CDC42EP1, CDC42EP2, CDC42EP3, CDC42EP4, CDC42EP5, CDC42SE1, CDC42SE2, PARD6A, PARD6B and PARD6G (in a GTP-dependent manner). Interacts with activated CSPG4 and with BAIAP2. Interacts with Zizimin1/DOCK9 and Zizimin2/DOCK11, which activate it by exchanging GDP for GTP. Interacts with NET1 and ARHGAP33/TCGAP. Part of a complex with PARD3, PARD6A or PARD6B and PRKCI or PRKCZ. Interacts with USP6. May interact with ARHGEF16; responsible for the activation of CDC42 by the viral protein HPV16 E6. Interacts with NEK6. Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas. Interacts with ITGB1BP1. Interacts with ARHGDIA; this interaction inactivates and stabilizes CDC42. Interacts with ARHGDIB; this maintains CDC42 in the inactive, GDP-bound form. Interacts in (GTP-bound form) with FNBP1L and ABI1, but only in the presence of FNBP1L (PubMed:19798448).By similarity17 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • apolipoprotein A-I receptor binding Source: BHF-UCL
  • GBD domain binding Source: CAFA
  • GTP-dependent protein binding Source: Ensembl
  • identical protein binding Source: IntAct
  • mitogen-activated protein kinase kinase kinase binding Source: Ensembl
  • protein kinase binding Source: BHF-UCL
  • Rho GDP-dissociation inhibitor binding Source: Ensembl
  • thioesterase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107433. 205 interactors.
DIPiDIP-31097N.
ELMiP60953.
IntActiP60953. 181 interactors.
MINTiMINT-94609.
STRINGi9606.ENSP00000314458.

Chemistry databases

BindingDBiP60953.

Structurei

Secondary structure

1191
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 11Combined sources10
Turni12 – 14Combined sources3
Helixi16 – 25Combined sources10
Helixi29 – 31Combined sources3
Beta strandi36 – 46Combined sources11
Beta strandi49 – 58Combined sources10
Helixi62 – 64Combined sources3
Turni65 – 67Combined sources3
Helixi68 – 71Combined sources4
Beta strandi72 – 74Combined sources3
Beta strandi76 – 83Combined sources8
Helixi87 – 95Combined sources9
Helixi97 – 104Combined sources8
Beta strandi105 – 107Combined sources3
Beta strandi110 – 115Combined sources6
Helixi117 – 121Combined sources5
Helixi123 – 130Combined sources8
Turni131 – 133Combined sources3
Helixi139 – 148Combined sources10
Beta strandi154 – 156Combined sources3
Turni159 – 161Combined sources3
Turni162 – 164Combined sources3
Helixi165 – 176Combined sources12
Beta strandi179 – 181Combined sources3
Turni184 – 186Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A4RX-ray2.50A/B1-191[»]
1AJENMR-A1-187[»]
1AM4X-ray2.70D/E/F2-177[»]
1AN0X-ray2.80A/B1-190[»]
1CEENMR-A1-179[»]
1CF4NMR-A1-184[»]
1DOAX-ray2.60A1-188[»]
1E0ANMR-A1-184[»]
1EESNMR-A1-178[»]
1GRNX-ray2.10A1-191[»]
1GZSX-ray2.30A/C1-178[»]
1KI1X-ray2.30A/C1-188[»]
1KZ7X-ray2.40B/D1-188[»]
1KZGX-ray2.60B/D1-188[»]
1NF3X-ray2.10A/B2-191[»]
2ASENMR-A1-178[»]
2DFKX-ray2.15B/D1-191[»]
2KB0NMR-A1-178[»]
2NGRX-ray1.90A1-191[»]
2ODBX-ray2.40A1-181[»]
2QRZX-ray2.40A/B1-189[»]
2WM9X-ray2.20B1-188[»]
2WMNX-ray2.39B1-188[»]
2WMOX-ray2.20B1-188[»]
3GCGX-ray2.30A2-178[»]
3QBVX-ray2.65A/C1-178[»]
3VHLX-ray2.08B1-188[»]
4DIDX-ray2.35A1-183[»]
4ITRX-ray2.30C/D1-191[»]
4JS0X-ray1.90A1-178[»]
4YC7X-ray2.50A1-179[»]
4YDHX-ray3.80B/D1-179[»]
5CJPX-ray2.60A/B/C/D1-177[»]
5FI1X-ray3.20B1-191[»]
5HZKX-ray3.30A/C1-181[»]
ProteinModelPortaliP60953.
SMRiP60953.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP60953.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 40Effector regionSequence analysis9

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0393. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00760000118978.
HOGENOMiHOG000233974.
HOVERGENiHBG009351.
InParanoidiP60953.
KOiK04393.
OMAiMQTLKCV.
OrthoDBiEOG091G0KCM.
PhylomeDBiP60953.
TreeFamiTF101109.

Family and domain databases

InterProiView protein in InterPro
IPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR003578. Small_GTPase_Rho.
PfamiView protein in Pfam
PF00071. Ras. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiView protein in PROSITE
PS51420. RHO. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: P60953-2) [UniParc]FASTAAdd to basket
Also known as: Placental

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQTIKCVVVG DGAVGKTCLL ISYTTNKFPS EYVPTVFDNY AVTVMIGGEP
60 70 80 90 100
YTLGLFDTAG QEDYDRLRPL SYPQTDVFLV CFSVVSPSSF ENVKEKWVPE
110 120 130 140 150
ITHHCPKTPF LLVGTQIDLR DDPSTIEKLA KNKQKPITPE TAEKLARDLK
160 170 180 190
AVKYVECSAL TQKGLKNVFD EAILAALEPP EPKKSRRCVL L
Length:191
Mass (Da):21,259
Last modified:February 8, 2011 - v2
Checksum:i51A437E22A4D8FFF
GO
Isoform 1 (identifier: P60953-1) [UniParc] [UniParc]FASTAAdd to basket
Also known as: Brain

The sequence of this isoform differs from the canonical sequence as follows:
     163-163: K → R
     182-191: PKKSRRCVLL → TQPKRKCCIF

Show »
Length:191
Mass (Da):21,311
Checksum:i34B44F9225EC106B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07633764Y → C in TKS. 2 PublicationsCorresponds to variant dbSNP:rs864309721Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_040583163K → R in isoform 1. 3 Publications1
Alternative sequenceiVSP_040584182 – 191PKKSRRCVLL → TQPKRKCCIF in isoform 1. 3 Publications10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M35543 mRNA. Translation: AAA52494.1.
M57298 mRNA. Translation: AAA52592.1.
AL121734 mRNA. Translation: CAB57325.1.
AL121735 mRNA. Translation: CAB57326.1.
AF498962 mRNA. Translation: AAM21109.1.
AF498963 mRNA. Translation: AAM21110.1.
AY673602 Genomic DNA. Translation: AAT70721.1.
AL031281 Genomic DNA. Translation: CAB52602.1.
AL031281 Genomic DNA. Translation: CAD92551.1.
BC002711 mRNA. Translation: AAH02711.1.
BC003682 mRNA. Translation: AAH03682.1.
BC018266 mRNA. Translation: AAH18266.1.
CCDSiCCDS221.1.
CCDS222.1. [P60953-1]
PIRiA36382.
A39265.
RefSeqiNP_001034891.1. NM_001039802.1. [P60953-2]
NP_001782.1. NM_001791.3. [P60953-2]
NP_426359.1. NM_044472.2. [P60953-1]
UniGeneiHs.467637.

Genome annotation databases

EnsembliENST00000315554; ENSP00000314458; ENSG00000070831. [P60953-1]
ENST00000344548; ENSP00000341072; ENSG00000070831. [P60953-2]
ENST00000400259; ENSP00000383118; ENSG00000070831. [P60953-2]
GeneIDi998.
KEGGihsa:998.
UCSCiuc001bfp.4. human.

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCDC42_HUMAN
AccessioniPrimary (citable) accession number: P60953
Secondary accession number(s): P21181
, P25763, Q7L8R5, Q9UDI2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: February 8, 2011
Last modified: August 30, 2017
This is version 176 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families