This pleckstrin homology (PH) domain is found in some Rho guanine nucleotide exchange factors, such as ARHGEF18 (p114RhoGEF) []and ARHGEF1 (p115-RhoGEF) [].
ARHGEF18 is a guanine nucleotide exchange factor that activates RhoA, a small GTPase protein that is a key component of tight junctions and adherens junctions []. It is crucial for maintenance of polarity in the vertebrate retinal epithelium, and consequently is essential for cellular differentiation, morphology and eventually organ function []. ARHGEF18 contains Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. This entry represents the PH domain of ARHGEF18.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner []. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity []. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane []. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes [].
