Alternative titles; symbols
HGNC Approved Gene Symbol: ARHGAP1
Cytogenetic location: 11p11.2 Genomic coordinates (GRCh38): 11:46,677,080-46,700,619 (from NCBI)
The Rho family of GTP-binding proteins modulates cytoskeletal changes. Garrett et al. (1991) purified a 29-kD cytoplasmic GTPase-activating protein (GAP), called RHOGAP by them, from human spleen extracts. RHOGAP stimulated the GTPase activity of p21-Rho but not other small molecular mass GTP-binding proteins. Diekmann et al. (1991) reported a partial amino acid sequence of RHOGAP. Using PCR with primers based on the RHOGAP protein sequence, Lancaster et al. (1994) isolated a human fibrosarcoma cell line cDNA encoding RHOGAP. Northern blot analysis revealed that RHOGAP is expressed as a 3.6-kb mRNA. The RHOGAP cDNA encodes a predicted 439-amino acid protein with a calculated molecular mass of 50 kD. Since antibodies against RHOGAP detected a 50-kD protein on Western blots of cell extracts, Lancaster et al. (1994) suggested that the previously observed 29-kD protein was a C-terminal proteolytic fragment of RHOGAP that was generated during protein purification.
Barfod et al. (1993) cloned human platelet-precursor cell cDNAs encoding CDC42GAP, a protein that inactivates CDC42 by stimulating GTP hydrolysis. They found that CDC42GAP contains a functional SH3-binding domain.
Lancaster et al. (1994) found that the Rho family members Rho, RAC, and CDC42 (116952) were substrates for RHOGAP, with CDC42 the preferred substrate.
Shen et al. (2008) showed that Nudel (NDEL1; 607538) colocalized with Cdc42gap at the leading edge of migrating NIH3T3 mouse fibroblasts. This localization of Nudel required its phosphorylation by Erk1 (MAPK3; 601795)/Erk2 (MAPK1; 176948). Shen et al. (2008) found that Nudel competed with Cdc42 for binding Cdc42gap. Consequently, Nudel inhibited Cdc42gap-mediated inactivation of Cdc42 in a dose-dependent manner. Depletion of Nudel by RNA interference or overexpression of a nonphosphorylatable Nudel mutant abolished Cdc42 activation and cell migration. Shen et al. (2008) concluded that NUDEL facilitates cell migration by sequestering CDC42GAP at the leading edge to stabilize active CDC42 in response to extracellular stimuli.
The International Radiation Hybrid Mapping Consortium mapped the RHOGAP1 gene to chromosome 11 (RH79109).
Barfod, E. T., Zheng, Y., Kuang, W.-J., Hart, M. J., Evans, T., Cerione, R. A., Ashkenazi, A. Cloning and expression of a human CDC42 GTPase-activating protein reveals a functional SH3-binding domain. J. Biol. Chem. 268: 26059-26062, 1993. [PubMed: 8253717]
Diekmann, D., Brill, S., Garrett, M. D., Totty, N., Hsuan, J., Monfries, C., Hall, C., Lim, L., Hall, A. Bcr encodes a GTPase-activating protein for p21-rac. Nature 351: 400-402, 1991. [PubMed: 1903516] [Full Text: https://doi.org/10.1038/351400a0]
Garrett, M. D., Major, G. N., Totty, N., Hall, A. Purification and N-terminal sequence of the p21-rho GTPase-activating protein, rho GAP. Biochem. J. 276: 833-836, 1991. [PubMed: 1905930] [Full Text: https://doi.org/10.1042/bj2760833]
Lancaster, C. A., Taylor-Harris, P. M., Self, A. J., Brill, S., van Erp, H. E., Hall, A. Characterization of rhoGAP: a GTPase-activating protein for rho-related small GTPases. J. Biol. Chem. 269: 1137-1142, 1994. [PubMed: 8288572]
Shen, Y., Li, N., Wu, S., Zhou, Y., Shan, Y., Zhang, Q., Ding, C., Yuan, Q., Zhao, F., Zeng, R., Zhu, X. Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells. Dev. Cell 14: 342-353, 2008. [PubMed: 18331715] [Full Text: https://doi.org/10.1016/j.devcel.2008.01.001]
Wildenberg, G. A., Dohn, M. R., Carnahan, R. H., Davis, M. A., Lobdell, N. A., Settleman, J., Reynolds, A. B. p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho. Cell 127: 1027-1039, 2006. [PubMed: 17129786] [Full Text: https://doi.org/10.1016/j.cell.2006.09.046]