PH domains can be found in many different proteins, such as
OSBP or
ARF. Recruitment to the
Golgi apparatus 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 contains two PH domains. ARAP proteins contain five PH domains. •
Serine/threonine-specific protein kinases such as the Akt/Rac family,
protein kinase D1, and the trypanosomal NrkA family. •
Non-receptor tyrosine kinases belonging to the Btk/Itk/Tec subfamily. • Insulin receptor substrate 1 (
IRS-1). • Regulators of
small G-proteins: 64 RhoGEFs of the Dbl-like family., and several GTPase activating proteins like ABR, BCR or ARAP proteins. • Cytoskeletal proteins such as
dynamin (see ),
Caenorhabditis elegans kinesin-like protein unc-104 (see ), spectrin beta-chain,
syntrophin (2 PH domains), and
S. cerevisiae nuclear migration protein NUM1. •
Oxysterol-binding proteins OSBP,
S. cerevisiae OSH1 and YHR073w. •
Ceramide kinase, a lipid kinase that phosphorylates
ceramides to ceramide-1-phosphate. == Clinical significance ==