Alternative titles; symbols
HGNC Approved Gene Symbol: ARHGAP5
Cytogenetic location: 14q12 Genomic coordinates (GRCh38): 14:32,077,304-32,159,728 (from NCBI)
Rho GTPase-activating proteins (Rho-GAPs) negatively regulate the Rho GTPases, a family which appears to mediate many cytoskeleton changes, by stimulating the hydrolysis of bound GTP. Burbelo et al. (1995) isolated human cDNAs with homology to the gene encoding rat p190 Rho-GAP. The predicted 1,499-amino acid human protein, designated p190B by the authors, has an N-terminal GTPase domain and a C-terminal Rho-GAP domain. The amino acid sequences of p190B and rat p190 are 51% identical. In vitro, the Rho-GAP domain of p190B showed GAP activity for several Rho GTPases, including RhoA (165390), RAC1 (602048), and CDC42 (116952). Immunoprecipitation and immunofluorescence studies showed that p190B was localized diffusely in the cytoplasm and in fibrillar patterns that colocalized with the ITGA5 (135620)-ITGB1 (135630) integrin receptor for fibronectin. By Northern blot analysis, Burbelo et al. (1995) detected 4.4- and 6.4-kb p190B transcripts in a variety of tissues.
Wildenberg et al. (2006) found that depletion of delta-catenin (CTNND1; 601045) in NIH3T3 mouse fibroblasts by small interfering RNA caused constitutive activation of Rho, cell transformation, loss of contact inhibition, and growth in the absence of serum. Moreover, Pdgf receptor (see 173490) and integrin signaling pathways involved in remodeling the actin cytoskeleton were selectively impaired. Wildenberg et al. (2006) traced these effects to obligatory roles of delta-catenin and Arhgap5 in a pathway that connects Rac activation to Rho inhibition. They concluded that delta-catenin and ARHGAP5 use Rho GTPases to mediate crosstalk between a wide variety of receptors to coordinate cadherin function with other activities that direct cell adhesion, motility, and proliferation.
The International Radiation Hybrid Mapping Consortium mapped the ARHGAP5 gene to chromosome 14 (RH91237).
Burbelo, P. D., Miyamoto, S., Utani, A., Brill, S., Yamada, K. M., Hall, A., Yamada, Y. p190-B, a new member of the Rho GAP family, and Rho are induced to cluster after integrin cross-linking. J. Biol. Chem. 270: 30919-30926, 1995. [PubMed: 8537347] [Full Text: https://doi.org/10.1074/jbc.270.52.30919]
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]