Pleckstrin Homology Domain - Proteins Containing PH Domain

Proteins Containing PH Domain

PH domains can be found in many different proteins, such as OSBP or 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. A Genome-wide look in Saccharomyces cerevisiae showed that most of the 33 yeast PH domains are indeed promiscuous in binding to phosphoinositides, while only one (Num1-PH) behaved highly specific . Proteins reported to contain 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 contain 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 S. 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.
• Ceramide kinase, a lipid kinase that phosphorylates ceramides to ceramide-1-phosphate.