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:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| TKS |
Biological Process
Actin cytoskeleton organization
Actin filament branching
Actin filament bundle assembly
Actin filament organization
Adherens junction organization
Axon guidance
Blood coagulation
Canonical Wnt signaling pathway
Cardiac conduction system development
Cdc42 protein signal transduction
Cell junction assembly
Cell migration
Cell projection assembly
Cellular protein localization
Cellular response to interferon-gamma
Cortical cytoskeleton organization
Dendritic cell migration
Dendritic spine morphogenesis
Endocytosis
Ephrin receptor signaling pathway
Epidermal growth factor receptor signaling pathway
Epithelial cell-cell adhesion
Epithelial-mesenchymal cell signaling
Establishment of epithelial cell apical/basal polarity
Establishment of Golgi localization
Establishment or maintenance of apical/basal cell polarity
Establishment or maintenance of cell polarity
Fc-gamma receptor signaling pathway involved in phagocytosis
Filopodium assembly
Golgi organization
Hair follicle morphogenesis
Hair follicle placode formation
Heart contraction
Innate immune response
Integrin-mediated signaling pathway
Interleukin-12-mediated signaling pathway
Keratinization
Keratinocyte development
Macrophage differentiation
Metabolic process
Modification of synaptic structure
Multicellular organism growth
Muscle cell differentiation
Negative regulation of epidermal growth factor receptor signaling pathway
Negative regulation of gene expression
Negative regulation of protein-containing complex assembly
Neuron fate determination
Neuropilin signaling pathway
Nuclear migration
Organelle transport along microtubule
Phagocytosis, engulfment
Positive regulation of actin cytoskeleton reorganization
Positive regulation of catalytic activity
Positive regulation of cell growth
Positive regulation of cytokinesis
Positive regulation of DNA replication
Positive regulation of epithelial cell proliferation involved in lung morphogenesis
Positive regulation of filopodium assembly
Positive regulation of gene expression
Positive regulation of hair follicle cell proliferation
Positive regulation of intracellular protein transport
Positive regulation of JNK cascade
Positive regulation of lamellipodium assembly
Positive regulation of muscle cell differentiation
Positive regulation of neuron apoptotic process
Positive regulation of peptidyl-serine phosphorylation
Positive regulation of phosphatidylinositol 3-kinase activity
Positive regulation of pinocytosis
Positive regulation of pseudopodium assembly
Positive regulation of stress fiber assembly
Positive regulation of substrate adhesion-dependent cell spreading
Positive regulation of synapse structural plasticity
Regulation of actin cytoskeleton organization
Regulation of attachment of spindle microtubules to kinetochore
Regulation of cell shape
Regulation of filopodium assembly
Regulation of lamellipodium assembly
Regulation of mitotic nuclear division
Regulation of modification of postsynaptic structure
Regulation of protein binding
Regulation of protein catabolic process
Regulation of protein heterodimerization activity
Regulation of protein kinase activity
Regulation of protein stability
Regulation of small GTPase mediated signal transduction
Regulation of stress fiber assembly
Rho protein signal transduction
Small GTPase mediated signal transduction
Sprouting angiogenesis
Submandibular salivary gland formation
Substantia nigra development
T cell costimulation
Vascular endothelial growth factor receptor signaling pathway
Viral RNA genome replication
Wnt signaling pathway, planar cell polarity pathway
Cellular Component
Apical part of cell
Cell cortex
Cell projection
Cell-cell junction
Cytoplasm
Cytoplasmic ribonucleoprotein granule
Cytoplasmic vesicle
Cytoskeleton
Cytosol
Dendritic spine
Endoplasmic reticulum membrane
Extracellular exosome
Filopodium
Focal adhesion
Golgi membrane
Golgi transport complex
Intracellular membrane-bounded organelle
Leading edge membrane
Membrane
Microtubule organizing center
Midbody
Mitotic spindle
Myelin sheath
Neuron projection
Neuronal cell body
Obsolete cell
Phagocytic vesicle
Plasma membrane
Protein complex
Protein-containing complex
Schaffer collateral - CA1 synapse
Secretory granule
Spindle midzone
Storage vacuole
Molecular Function
Apolipoprotein A-I receptor binding
G protein activity
GBD domain binding
GTP binding
GTP-dependent protein binding
GTPase activity
Identical protein binding
Mitogen-activated protein kinase kinase kinase binding
Protein kinase binding
Protein serine/threonine kinase activity
Rho GDP-dissociation inhibitor binding
Thioesterase binding
Ubiquitin protein ligase activity
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
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