InterPro: IPR001849 Pleckstrin homology

The 'pleckstrin homology' (PH) domain is a domain of about 100 residues that occurs in a wide range of proteins involved in intracellular signalling or as constituents of the cytoskeleton [1, 2, 3, 4, 5, 6, 7].

The function of this domain is not clear, several putative functions have been suggested:

It is possible that different PH domains have totally different ligand requirements.

The 3D structure of several PH domains has been determined [8]. All known cases have a common structure consisting of two perpendicular anti-parallel beta sheets, followed by a C-terminal amphipathic helix. The loops connecting the beta-strands differ greatly in length, making the PH domain relatively difficult to detect. There are no totally invariant residues within the PH domain.

Proteins reported to contain one more PH domains belong to the following families:

• Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. Pleckstrin is one of the rare proteins to contains two PH domains.
• Ser/Thr protein kinases such as the Akt/Rac family, the beta-adrenergic receptor kinases, the mu isoform of PKC and the trypanosomal NrkA family.
• Tyrosine protein kinases belonging to the Btk/Itk/Tec subfamily.
• Insulin Receptor Substrate 1 (IRS-1).
• Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr.
• Cytoskeletal proteins such as dynamin (see IPR001401), Caenorhabditis elegans kinesin-like protein unc-104 (see IPR001752), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1.
• Mammalian phosphatidylinositol-specific phospholipase C (PI-PLC) (see IPR000909) isoforms gamma and delta. Isoform gamma contains two PH domains, the second one is split into two parts separated by about 400 residues.
• Oxysterol binding proteins OSBP, S. cerevisiae OSH1 and YHR073w.
• Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac.
Several S. cerevisiae proteins involved in cell cycle regulation and bud formation like BEM2, BEM3, BUD4 and the BEM1-binding proteins BOI2 (BEB1) and BOI1 (BOB1).
• C. elegans protein MIG-10.
• C. elegans hypothetical proteins C04D8.1, K06H7.4 and ZK632.12.
• S. cerevisiae hypothetical proteins YBR129c and YHR155w.