InterPro domain: IPR011993

Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of signalling proteins, where they serve as simple targeting domains that bind lipids [ 1 , 2 , 3 ].

PH domains have a partly opened beta-barrel topology that is capped by an alpha helix. The structure of PH domains is similar to the phosphotyrosine-binding domain (PTB) found in IRS-1 (insulin receptor substrate 1) [ 4 ], Shc adaptor and Numb [ 5 ]; to the Ran-binding domain, found in Nup nuclear pore complex and Ranbp1 [ 6 ]; to the Enabled/VASP homology domain 1 (EVH1 domain), found in Enabled, VASP (vasodilator-stimulated phosphoprotein), Homer and WASP actin regulatory protein [ 7 ]; and to the third domain of FERM, found in moesin, radixin, ezrin, merlin and talin [ 8 ].

This superfamily represents the PH domain and structurally related domains.

1. Membrane targeting by pleckstrin homology domains. Curr. Top. Microbiol. Immunol. 282, 49-88
2. Phosphoinositide recognition domains. Traffic 4, 201-13
3. A systematic screen for protein-lipid interactions in Saccharomyces cerevisiae. Mol. Syst. Biol. 6, 430
4. Structure of the IRS-1 PTB domain bound to the juxtamembrane region of the insulin receptor. Cell 85, 695-705
5. Structural and evolutionary division of phosphotyrosine binding (PTB) domains. J. Mol. Biol. 345, 1-20
6. Structure of a Ran-binding domain complexed with Ran bound to a GTP analogue: implications for nuclear transport. Nature 398, 39-46
7. 1.15 A crystal structure of the X. tropicalis Spred1 EVH1 domain suggests a fourth distinct peptide-binding mechanism within the EVH1 family. FEBS Lett. 579, 1161-6
8. Structure of the active N-terminal domain of Ezrin. Conformational and mobility changes identify keystone interactions. J. Biol. Chem. 278, 4949-56