CDC42

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 (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).

Involvement in disease

Takenouchi-Kosaki syndrome

TKS

A syndrome characterized by macrothrombocytopenia, lymphedema, mental retardation, developmental delay, and distinctive facial features.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

(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.

Phosphorylated by SRC in an EGF-dependent manner, this stimulates the binding of the Rho-GDP dissociation inhibitor RhoGDI.

(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.

(Microbial infection) Glucosylated at Thr-35 by C.difficile toxins TcdA and TcdB in the colonic epithelium (PubMed:7777059, PubMed:7775453, PubMed:24905543). Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption and cell death, resulting in the loss of colonic epithelial barrier function (PubMed:7777059, PubMed:7775453).

(Microbial infection) Glycosylated (O-GlcNAcylated) at Thr-35 by C.novyi toxin TcdA (PubMed:8810274). O-GlcNAcylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption (PubMed:8810274).

Sequence similarities

Belongs to the small GTPase superfamily. Rho family. CDC42 subfamily.

Cellular localization

• Cell membrane
• Lipid-anchor
• Cytoplasmic side
• Cytoplasm
• Cytoskeleton
• Microtubule organizing center
• Centrosome
• Cytoplasm
• Cytoskeleton
• Spindle
• Midbody
• Cell projection
• Dendrite
• Localizes to spindle during prometaphase cells. Moves to the central spindle as cells progressed through anaphase to telophase (PubMed:15642749). Localizes at the end of cytokinesis in the intercellular bridge formed between two daughter cells (PubMed:15642749). Its localization is regulated by the activities of guanine nucleotide exchange factor ECT2 and GTPase activating protein RACGAP1 (PubMed:15642749). Colocalizes with NEK6 in the centrosome (PubMed:20873783). In its active GTP-bound form localizes to the leading edge membrane of migrating dendritic cells (By similarity).

Alternative names

• Cell division control protein 42 homolog
• G25K GTP-binding protein
• CDC42

Database links

• entrezGene:998
• omim:116952
• swissprot:P60953

Target type

Proteins

Molecular weight

21259Da