PROSITE documentation PDOC51852

pG1 and pG2 pseudoGTPase domains profiles

GTPases bind to guanosine triphosphate (GTP), hydrolyze γ-phosphate, release guanosine diphosphate (GDP) and then rebind GTP, a process termed 'GTPase cycling'. This cycling, and consequent signal transduction, is regulated by GTPase activating proteins (GAPs) (for GTP hydrolysis) and guanine nucleotide exchange factors (GEFs) (for GDP release). The Ras superfamily of small GTPases consists of five subgroups (Ras, Rho, Rab, Ran and Arf) that act as molecular switches in broad and diverse cellular pathways and processes. Small GTPases in the Rho subgroup (including RhoA, Cdc42 and Rac1) mediate signaling from the cell membrane to the actin cytoskeleton and play key roles in cellular functions such as adhesion, migration and cytokinesis, and in disease-associated processes such as cell growth and metastasis in cancer. The p190RhoGAP proteins, p190RhoGAP-A (ARHGAP35) and p190RhoGAP-B ((ARHGAP5), are key regulators of Rho GTP hydrolysis and are highly important for maintenance of proper Rho signaling. They share a domain organization containing a GTP-binding GTPase domain, four FF domains, two GTPase-like folds (pG1 and pG2) and a C-terminal GAP domain [1].

The pG1 pseudoGTPase domain adopts a small GTPase fold, with a central 6-stranded β-sheet surrounded by four α-helices (see <PDB:5U4U>). The conserved GTPase motifs from the pG1 pseudoGTPase domain, which is not a nucleotide-binding domain.

Similar to pG1, the five G motifs of the pG2 pseudoGTPase are highly degraded.

The profiles we developed cover the entire pG1 and pG2 pseudoGTPase domains.