Cell division control protein 42 homolog (CDC42)

The protein contains 191 amino acids for an estimated molecular weight of 21259 Da.

 

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 (PubMed:15642749). Regulates cell migration (PubMed:17038317). In neurons, plays a role in the extension and maintenance of the formation of filopodia, thin and actin-rich surface projections (PubMed:14978216). Required for DOCK10-mediated spine formation in Purkinje cells and hippocampal neurons. Facilitates filopodia formation upon DOCK11-activation (By similarity). Upon activation by CaMKII, modulates dendritic spine structural plasticity by relaying CaMKII transient activation to synapse-specific, long-term signaling (By similarity). Also plays a role in phagocytosis through organization of the F-actin cytoskeleton associated with forming phagocytic cups (PubMed:26465210). (updated: July 3, 2019)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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VariantDescription
TKS

Biological Process

Actin cytoskeleton organization GO Logo
Actin filament branching GO Logo
Actin filament bundle assembly GO Logo
Actin filament organization GO Logo
Adherens junction organization GO Logo
Axon guidance GO Logo
Blood coagulation GO Logo
Canonical Wnt signaling pathway GO Logo
Cardiac conduction system development GO Logo
Cdc42 protein signal transduction GO Logo
Cell junction assembly GO Logo
Cell migration GO Logo
Cell projection assembly GO Logo
Cellular protein localization GO Logo
Cellular response to interferon-gamma GO Logo
Cortical cytoskeleton organization GO Logo
Dendritic cell migration GO Logo
Dendritic spine morphogenesis GO Logo
Endocytosis GO Logo
Ephrin receptor signaling pathway GO Logo
Epidermal growth factor receptor signaling pathway GO Logo
Epithelial cell-cell adhesion GO Logo
Epithelial-mesenchymal cell signaling GO Logo
Establishment of epithelial cell apical/basal polarity GO Logo
Establishment of Golgi localization GO Logo
Establishment or maintenance of apical/basal cell polarity GO Logo
Establishment or maintenance of cell polarity GO Logo
Fc-gamma receptor signaling pathway involved in phagocytosis GO Logo
Filopodium assembly GO Logo
Golgi organization GO Logo
Hair follicle morphogenesis GO Logo
Hair follicle placode formation GO Logo
Heart contraction GO Logo
Innate immune response GO Logo
Integrin-mediated signaling pathway GO Logo
Interleukin-12-mediated signaling pathway GO Logo
Keratinization GO Logo
Keratinocyte development GO Logo
Macrophage differentiation GO Logo
Metabolic process GO Logo
Modification of synaptic structure GO Logo
Multicellular organism growth GO Logo
Muscle cell differentiation GO Logo
Negative regulation of epidermal growth factor receptor signaling pathway GO Logo
Negative regulation of gene expression GO Logo
Negative regulation of protein-containing complex assembly GO Logo
Neuron fate determination GO Logo
Neuropilin signaling pathway GO Logo
Nuclear migration GO Logo
Organelle transport along microtubule GO Logo
Phagocytosis, engulfment GO Logo
Positive regulation of actin cytoskeleton reorganization GO Logo
Positive regulation of catalytic activity GO Logo
Positive regulation of cell growth GO Logo
Positive regulation of cytokinesis GO Logo
Positive regulation of DNA replication GO Logo
Positive regulation of epithelial cell proliferation involved in lung morphogenesis GO Logo
Positive regulation of filopodium assembly GO Logo
Positive regulation of gene expression GO Logo
Positive regulation of hair follicle cell proliferation GO Logo
Positive regulation of intracellular protein transport GO Logo
Positive regulation of JNK cascade GO Logo
Positive regulation of lamellipodium assembly GO Logo
Positive regulation of muscle cell differentiation GO Logo
Positive regulation of neuron apoptotic process GO Logo
Positive regulation of peptidyl-serine phosphorylation GO Logo
Positive regulation of phosphatidylinositol 3-kinase activity GO Logo
Positive regulation of pinocytosis GO Logo
Positive regulation of pseudopodium assembly GO Logo
Positive regulation of stress fiber assembly GO Logo
Positive regulation of substrate adhesion-dependent cell spreading GO Logo
Positive regulation of synapse structural plasticity GO Logo
Regulation of actin cytoskeleton organization GO Logo
Regulation of attachment of spindle microtubules to kinetochore GO Logo
Regulation of cell shape GO Logo
Regulation of filopodium assembly GO Logo
Regulation of lamellipodium assembly GO Logo
Regulation of mitotic nuclear division GO Logo
Regulation of modification of postsynaptic structure GO Logo
Regulation of protein binding GO Logo
Regulation of protein catabolic process GO Logo
Regulation of protein heterodimerization activity GO Logo
Regulation of protein kinase activity GO Logo
Regulation of protein stability GO Logo
Regulation of small GTPase mediated signal transduction GO Logo
Regulation of stress fiber assembly GO Logo
Rho protein signal transduction GO Logo
Small GTPase mediated signal transduction GO Logo
Sprouting angiogenesis GO Logo
Submandibular salivary gland formation GO Logo
Substantia nigra development GO Logo
T cell costimulation GO Logo
Vascular endothelial growth factor receptor signaling pathway GO Logo
Viral RNA genome replication GO Logo
Wnt signaling pathway, planar cell polarity pathway GO Logo

The reference OMIM entry for this protein is 116952

Cell division cycle 42; cdc42
Gtp-binding protein, 25-kd; g25k

DESCRIPTION

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

CLONING

Shinjo et al. (1990) isolated cDNA clones that code for cdc42, a low molecular weight GTP-binding protein originally designated G(p) and also called G25K, from a human placenta library. The predicted amino acid sequence of the protein was very similar to those of various members of the RAS superfamily of low molecular weight GTP-binding proteins, including NRAS, KRAS, HRAS, and the RHO proteins. The highest degree of sequence identity (80%) was found with the Saccharomyces cerevisiae cell division cycle protein CDC42. The human placental gene complemented a cdc42 mutation in S. cerevisiae. Munemitsu et al. (1990) presented further evidence that G25K is the human homolog of the CDC42 gene product. Marks and Kwiatkowski (1996) identified 2 isoforms of mouse Cdc42. They demonstrated that the 2 murine isoforms arise from a single gene by alternative splicing. Although one is expressed in a wide variety of tissues, the second isoform appeared to be expressed exclusively in brain.

GENE FUNCTION

Erickson et al. (1996) used cell fractionation and immunofluorescence to show that cdc42 is localized to the Golgi apparatus of mammalian cells. It colocalizes with the nonclathrin coat proteins ARF3 (103190) and COPB (600959) and its Golgi localization is disrupted by the drug brefeldin A. Based on their findings, Erickson et al. (1996) suggested that cdc42 may be involved in the delivery of newly synthesized proteins and lipids to the plasma membrane and that the GTP-binding/GTPase cycle may dictate its subcellular localization. By screening rat brain cytosol for proteins that interacted with Ras-related GTPases, or p21 proteins, of the Rho (RHOA; 165390) subfamily, Manser et al. (1994) identified 3 proteins, designated PAKs (see PAK1; 602590) that interacted with the GTP-bound forms of human CDC42 and RAC1 (602048), but not RHOA. Brown et al. (1996) found that activity of human PAK1 was induced by coexpression with RAC1 or CDC42. Zheng et al. (1996) reported that the FGD1 protein (305400) acts as a cdc42-specific GDP-GTP exchange factor. Cells expressing a fragment of the FGD1 protein encompassing the pleckstrin and Dbl homology domains activated 2 elements downstream of cdc42, namely, Jun kinase (165160) and p70 S6 kinase. Manser et al. (1993) identified ACK1 (606994) as a binding partner and inhibitor of the GTP-bound form of CDC42. Interaction between GTP-CDC42 and ACK1 inhibited both the intrinsic and GAP-stimulated GTPase activity of CDC42. CDC42 can regulate the actin cytoskeleton through activation of WASP family members (see 301000). Activation relieves an autoinhibitory contact between the GTPase-binding domain and the C-terminal region of WASP proteins. Kim et al. (2000) reported the autoinhibited structure of the GTPase-binding domain of WASP, which can be induced by the C-terminal region or by organic cosolvents. In the autoinhibited complex, intramolecular interactions with the GTPase-binding domain occlude residues of the C terminus that regulate the Arp2/3 actin-nucleating complex (see 604221). Binding of CDC42 to the GTPase-binding domain causes a dramatic conformat ... More on the omim web site

Subscribe to this protein entry history

July 4, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 116952 was added.

Jan. 27, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed