P60766 (CDC42_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cell division control protein 42 homolog

Alternative name(s):
G25K GTP-binding protein

Gene names

Name:

Cdc42

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	191 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Enzyme regulation	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.
Subunit structure	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. The GTP-bound form interacts with CCPG1. Interacts with USP6 By similarity. Interacts with NEK6 By similarity. Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas By similarity. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side Potential. Midbody By similarity. Cytoplasm › cytoskeleton › centrosome By similarity. Note: Localizes to spindle during prometaphase cells. Moves to the central spindle as cells progressed through anaphase to telophase. Localizes at the end of cytokinesis in the intercellular bridge formed between two daughter cells. Its localization is regulated by the activities of guanine nucleotide exchange factor ECT2 and GTPase activating protein RACGAP1. Colocalizes with NEK6 in the centrosome By similarity.
Sequence similarities	Belongs to the small GTPase superfamily. Rho family. CDC42 subfamily.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Alternative splicing
Ligand	GTP-binding Nucleotide-binding
PTM	Acetylation Lipoprotein Methylation Prenylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	Rho protein signal transduction Traceable author statement Ref.8. Source: MGI actin filament bundle assembly Inferred from mutant phenotype. Source: MGI adherens junction organization Inferred from mutant phenotype. Source: MGI canonical Wnt receptor signaling pathway Inferred from mutant phenotype. Source: MGI cellular protein localization Inferred from mutant phenotype. Source: MGI endosome transport Traceable author statement. Source: UniProtKB epithelial cell-cell adhesion Inferred from mutant phenotype. Source: MGI epithelial-mesenchymal cell signaling Inferred from mutant phenotype. Source: MGI establishment or maintenance of apical/basal cell polarity Inferred from mutant phenotype. Source: MGI filopodium assembly Inferred from direct assay. Source: MGI hair follicle morphogenesis Inferred from mutant phenotype. Source: MGI hair follicle placode formation Inferred from mutant phenotype. Source: MGI keratinization Inferred from mutant phenotype. Source: MGI keratinocyte development Inferred from mutant phenotype. Source: MGI multicellular organism growth Inferred from mutant phenotype. Source: MGI negative regulation of gene expression Inferred from mutant phenotype. Source: MGI neuron fate determination Inferred from mutant phenotype. Source: MGI nuclear migration Inferred from mutant phenotype. Source: MGI positive regulation of cell cycle cytokinesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of gene expression Inferred from mutant phenotype. Source: MGI positive regulation of hair follicle cell proliferation Inferred from mutant phenotype. Source: MGI positive regulation of peptidyl-serine phosphorylation Inferred from mutant phenotype. Source: MGI positive regulation of phosphatidylinositol 3-kinase activity Inferred from mutant phenotype. Source: MGI regulation of attachment of spindle microtubules to kinetochore Inferred from sequence or structural similarity. Source: UniProtKB regulation of filopodium assembly Inferred from sequence or structural similarity. Source: UniProtKB regulation of mitosis Inferred from mutant phenotype. Source: MGI regulation of protein catabolic process Inferred from mutant phenotype. Source: MGI regulation of protein heterodimerization activity Inferred from direct assay. Source: MGI regulation of protein kinase activity Inferred from mutant phenotype. Source: MGI regulation of protein stability Inferred from mutant phenotype. Source: MGI
Cellular component	apical part of cell Inferred from direct assay. Source: MGI cytosol Traceable author statement. Source: Reactome microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell midbody Inferred from sequence or structural similarity. Source: UniProtKB mitotic spindle Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell spindle midzone Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	GTP binding Inferred from direct assay. Source: MGI GTP-dependent protein binding Inferred from physical interaction. Source: UniProtKB GTPase activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Vamp2	P63044	2	EBI-81763,EBI-521920

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: P60766-2)

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.

Isoform 1 (identifier: P60766-1)

Also known as: Brain;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 188

188

Cell division control protein 42 homolog

PRO_0000030427

Propeptide

189 – 191

3

Removed in mature form By similarity

PRO_0000030428

Regions

Nucleotide binding

10 – 17

8

GTP By similarity

Nucleotide binding

57 – 61

5

GTP By similarity

Nucleotide binding

115 – 118

4

GTP By similarity

Motif

32 – 40

9

Effector region Potential

Amino acid modifications

Modified residue

135

1

N6-acetyllysine By similarity

Modified residue

144

1

N6-acetyllysine By similarity

Modified residue

188

1

Cysteine methyl ester By similarity

Lipidation

188

1

S-geranylgeranyl cysteine By similarity

Natural variations

Alternative sequence

163

1

K → R in isoform 1.

VSP_040585

Alternative sequence

182 – 191

10

PKKSRRCVLL → TQPKRKCCIF in isoform 1.

VSP_040586

Experimental info

Mutagenesis

17

1

T → N: Constitutively inactivated. Abolishes interaction with PARD6 and DOCK11. Ref.9 Ref.13

Mutagenesis

61

1

Q → L: Constitutively activated. Enhances interaction with DOCK11. Ref.13

Sequence conflict

26

1

N → D in BAC34669. Ref.4

Sequence conflict

66

1

R → G in AAH64792. Ref.6

Sequence conflict

85

1

V → I in BAE39489. Ref.4

Sequence conflict

116

1

Q → K in BAE40049. Ref.4

Sequence conflict

171

1

E → G in AAH64792. Ref.6

Secondary structure

1

.

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191

Helix Strand Turn

Details...

Beta strand

6 – 9

4

Helix

17 – 25

9

Beta strand

36 – 45

10

Beta strand

50 – 53

4

Beta strand

55 – 58

4

Helix

62 – 64

3

Turn

65 – 67

3

Helix

68 – 71

4

Beta strand

76 – 81

6

Helix

87 – 95

9

Helix

97 – 104

8

Beta strand

110 – 113

4

Helix

117 – 119

3

Helix

123 – 131

9

Helix

139 – 148

10

Turn

159 – 161

3

Helix

166 – 177

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (Placental) [UniParc]. Last modified February 8, 2011. Version 2. Checksum: 51A437E22A4D8FFF	FASTA	191	21,259
	10 20 30 40 50 60 MQTIKCVVVG DGAVGKTCLL ISYTTNKFPS EYVPTVFDNY AVTVMIGGEP YTLGLFDTAG 70 80 90 100 110 120 QEDYDRLRPL SYPQTDVFLV CFSVVSPSSF ENVKEKWVPE ITHHCPKTPF LLVGTQIDLR 130 140 150 160 170 180 DDPSTIEKLA KNKQKPITPE TAEKLARDLK AVKYVECSAL TQKGLKNVFD EAILAALEPP 190 EPKKSRRCVL L
	Isoform 1 (Brain) [UniParc] [UniParc]. Checksum: 34B44F9225EC106B	FASTA	191	21,311
	10 20 30 40 50 60 MQTIKCVVVG DGAVGKTCLL ISYTTNKFPS EYVPTVFDNY AVTVMIGGEP YTLGLFDTAG 70 80 90 100 110 120 QEDYDRLRPL SYPQTDVFLV CFSVVSPSSF ENVKEKWVPE ITHHCPKTPF LLVGTQIDLR 130 140 150 160 170 180 DDPSTIEKLA KNKQKPITPE TAEKLARDLK AVKYVECSAL TQRGLKNVFD EAILAALEPP 190 ETQPKRKCCI F

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Oncogene ect2 is related to regulators of small GTP-binding proteins." Miki T., Smith C.L., Long J.E., Eva A., Fleming T.P. Nature 362:462-465(1993) [PubMed: 8464478] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"Complete cDNAs for CDC42 from chicken cochlea and mouse liver." Gong T.W., Shin J.J., Burmeister M., Lomax M.I. Biochim. Biophys. Acta 1352:282-292(1997) [PubMed: 9224952] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Liver.
[3]	"Genomic organization and chromosomal location of murine Cdc42." Marks P.W., Kwiatkowski D.J. Genomics 38:13-18(1996) [PubMed: 8954774] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). Strain: C57BL/6. Tissue: Brain.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: BALB/c, C57BL/6J, DBA/2 and NOD. Tissue: Amnion, Bone marrow, Heart, Kidney, Liver, Mammary gland, Placenta, Spinal ganglion and Thymus.
[5]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Embryonic germ cell.
[7]	Lubec G., Klug S. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 108-120, MASS SPECTROMETRY. Tissue: Hippocampus.
[8]	"The Borgs, a new family of Cdc42 and TC10 GTPase-interacting proteins." Joberty G., Perlungher R.R., Macara I.G. Mol. Cell. Biol. 19:6585-6597(1999) [PubMed: 10490598] [Abstract] Cited for: INTERACTION WITH CDC42EP4.
[9]	"The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42." Joberty G., Petersen C., Gao L., Macara I.G. Nat. Cell Biol. 2:531-539(2000) [PubMed: 10934474] [Abstract] Cited for: SUBUNIT OF A COMPLEX CONTAINING PARD6B; PARD3 AND PRKCZ, MUTAGENESIS OF THR-17.
[10]	"Analysis of RhoA-binding proteins reveals an interaction domain conserved in heterotrimeric G protein beta subunits and the yeast response regulator protein Skn7." Alberts A.S., Bouquin N., Johnston L.H., Treisman R. J. Biol. Chem. 273:8616-8622(1998) [PubMed: 9535835] [Abstract] Cited for: INTERACTION WITH NET1.
[11]	"TCGAP, a multidomain Rho GTPase-activating protein involved in insulin-stimulated glucose transport." Chiang S.-H., Hwang J., Legendre M., Zhang M., Kimura A., Saltiel A.R. EMBO J. 22:2679-2691(2003) [PubMed: 12773384] [Abstract] Cited for: INTERACTION WITH ARHGAP33/TCGAP.
[12]	"Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes." Nishikimi A., Meller N., Uekawa N., Isobe K., Schwartz M.A., Maruyama M. FEBS Lett. 579:1039-1046(2005) [PubMed: 15710388] [Abstract] Cited for: INTERACTION WITH DOCK11.
[13]	"Identification of a DOCK180-related guanine nucleotide exchange factor that is capable of mediating a positive feedback activation of Cdc42." Lin Q., Yang W., Baird D., Feng Q., Cerione R.A. J. Biol. Chem. 281:35253-35262(2006) [PubMed: 16968698] [Abstract] Cited for: INTERACTION WITH DOCK11 AND IQGAP1, MUTAGENESIS OF THR-17 AND GLN-61.
[14]	"Ccpg1, a novel scaffold protein that regulates the activity of the Rho guanine nucleotide exchange factor Dbs." Kostenko E.V., Olabisi O.O., Sahay S., Rodriguez P.L., Whitehead I.P. Mol. Cell. Biol. 26:8964-8975(2006) [PubMed: 17000758] [Abstract] Cited for: INTERACTION WITH CCPG1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L11318 mRNA. Translation: AAA37410.1.
U37720 mRNA. Translation: AAC00028.1.
L78075 Genomic DNA. Translation: AAB40051.1.
AK003098 mRNA. Translation: BAB22563.1.
AK051543 mRNA. Translation: BAC34669.1.
AK075567 mRNA. Translation: BAC35825.1.
AK144216 mRNA. Translation: BAE25778.1.
AK151087 mRNA. Translation: BAE30100.1.
AK151726 mRNA. Translation: BAE30644.1.
AK153564 mRNA. Translation: BAE32098.1.
AK154870 mRNA. Translation: BAE32891.1.
AK159470 mRNA. Translation: BAE35111.1.
AK166281 mRNA. Translation: BAE38678.1.
AK167195 mRNA. Translation: BAE39325.1.
AK167400 mRNA. Translation: BAE39489.1.
AK167609 mRNA. Translation: BAE39663.1.
AK168013 mRNA. Translation: BAE40000.1.
AK168076 mRNA. Translation: BAE40049.1.
AK168089 mRNA. Translation: BAE40062.1.
AK168276 mRNA. Translation: BAE40222.1.
AK168758 mRNA. Translation: BAE40595.1.
AK168820 mRNA. Translation: BAE40647.1.
AK169122 mRNA. Translation: BAE40902.1.
AK169232 mRNA. Translation: BAE41001.1.
AK169805 mRNA. Translation: BAE41379.1.
AL645468 Genomic DNA. Translation: CAM18513.1.
AL645468 Genomic DNA. Translation: CAM18514.1.
BC064792 mRNA. Translation: AAH64792.1.

IPI

IPI00113849.
IPI00120193.

RefSeq

NP_001230698.1. NM_001243769.1.
NP_033991.1. NM_009861.3.

UniGene

Mm.1022.
Mm.447553.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EG5	X-ray	2.70	A/C	1-178	[»]

ProteinModelPortal

P60766.

SMR

P60766. Positions 1-191.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-32554N.

IntAct

P60766. 10 interactions.

MINT

MINT-1602743.

STRING

P60766.

PTM databases

PhosphoSite

P60766.

Proteomic databases

PRIDE

P60766.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000030417; ENSMUSP00000030417; ENSMUSG00000006699.
ENSMUST00000051477; ENSMUSP00000054634; ENSMUSG00000006699.
ENSMUST00000171333; ENSMUSP00000127086; ENSMUSG00000006699.

GeneID

12540.

KEGG

mmu:12540.

UCSC

uc008viw.2. mouse.
uc008viy.1. mouse.

Organism-specific databases

CTD

998.

MGI

MGI:106211. Cdc42.

Phylogenomic databases

eggNOG

roNOG07751.

HOVERGEN

HBG009351.

OMA

EITHHCQ.

OrthoDB

EOG4R23VV.

PhylomeDB

P60766.

Enzyme and pathway databases

Reactome

REACT_115492. Developmental Biology.

Gene expression databases

ArrayExpress

P60766.

Bgee

P60766.

CleanEx

MM_CDC42.

Genevestigator

P60766.

GermOnline

ENSMUSG00000006699. Mus musculus.

Family and domain databases

InterPro

IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR003578. Small_GTPase_Rho.
[Graphical view]

KO

K04393.

Pfam

PF00071. Ras. 1 hit.
[Graphical view]

PRINTS

PR00449. RASTRNSFRMNG.

SMART

SM00174. RHO. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00231. Small_GTP. 1 hit.

PROSITE

PS51420. RHO. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

281582.

SOURCE

Search...

Entry information

Entry name

CDC42_MOUSE

Accession

Primary (citable) accession number: P60766
Secondary accession number(s): A2A9U6 , P21181, P25763, Q3THZ7, Q3TJK6, Q545V0, Q6P201, Q8BQ51

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	February 8, 2011
Last modified:	November 16, 2011
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program