Gene Summary: The protein encoded by this CDC42 gene is a small GTPase of the Rho-subfamily, which regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis and cell cycle progression. This CDC42 protein is highly similar to Saccharomyces cerevisiae CDC42, and is able to complement the yeast cdc42-1 mutant. The product of oncogene Dbl was reported to specifically catalyze the dissociation of GDP from this protein. This CDC42 protein could regulate actin polymerization through its direct binding to Neural Wiskott-Aldrich syndrome protein (N-WASP), which subsequently activates Arp2/3 complex. Alternative splicing of this CDC42 gene results in multiple transcript variants.General information above from NCBI
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: 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.
Subcellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential). Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle. Midbody. 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.
Post-translational: 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.
Sequence similarity: Belongs to the small GTPase superfamily. Rho family. CDC42 subfamily.
General information above from UniProt
Shinjo K, et al. (1990) Molecular cloning of the gene for the human placental GTP-binding protein Gp (G25K): identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42. Proc Natl Acad Sci. 87(24):9853-7.
Munemitsu S, et al. (1990) Molecular cloning and expression of a G25K cDNA, the human homolog of the yeast cell cycle gene CDC42. Mol Cell Biol. 10(11):5977-82.
Walker S J, et al. (2000) Activation of phospholipase D1 by Cdc42 requires the Rho insert region. J Biol Chem. 275(21):15665-8.
Low B C, et al. (1999) Tyrosine phosphorylation of the Bcl-2-associated protein BNIP-2 by fibroblast growth factor receptor-1 prevents its binding to Cdc42GAP and Cdc42. J Biol Chem. 274(46): 33123-30.
Zhang B, et al. (1998) Interaction of Rac1 with GTPase-activating proteins and putative effectors. A comparison with Cdc42 and RhoA. J Biol Chem. 273(15):8776-82.