Pleckstrin homology domain

Pleckstrin homology domain (PH domain) is a protein region of approximately 120 amino acids that can bind Phosphatidylinositol lipids within biological membranes (such as Phosphatidylinositol (3,4,5)-trisphosphate and phosphatidylinositol (4,5)-bisphosphate), and proteins such as the βγ-subunits of heterotrimeric G proteins and protein kinase C. Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartment or enabling them to interact with other components of the signal transduction pathways.

Individual PH domains possess specificities for phosphoinositides phosphorylated at different sites within the inositol ring, ie some bind phosphatidylinositol (4,5)-bisphosphate but not Phosphatidylinositol (3,4,5)-trisphosphate or Phosphatidylinositol (3,4)-bisphosphate or vice versa. This is important because it makes the recruitment of different PH domain containing proteins sensitive to the activities of enzymes that either phosphorylate or dephosphorylate these sites on the inositol ring, such as phosphoinositide 3-kinase or PTEN, respectively. Thus, such enzymes exert a part of their effect on cell function by modulating the localization of downstream signaling proteins that possess PH domains that are capable of binding their phospho-lipid products.

The unrelated FYVE domain binds Phosphatidylinositol 3-phosphate and has been found in over 60 proteins.

Other interactions
PH domains can also bind to other proteins, for example the PH domain of OSBP to ARF. Recruitment to the Golgi in this case is dependent on both PtdIns and ARF. A large number of PH domains have poor affinity for phosphoinositides and are hypothesized to function as protein binding domains.