To improve security and privacy, we are moving our web pages and services from HTTP to HTTPS. To give users of web services time to transition to HTTPS, we will support separate HTTP and HTTPS services until the end of 2017. From January 2018 most HTTP traffic will be automatically redirected to HTTPS. [more...] View this page in https
The 'pleckstrin homology' (PH) domain is a domain of about 100 residues that
occurs in a wide range of proteins involved in intracellular signaling 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
binding to the β/γ subunit of heterotrimeric G proteins,
binding to lipids, e.g. phosphatidylinositol-4,5-bisphosphate,
binding to phosphorylated Ser/Thr residues,
attachment to membranes by an unknown mechanism.
It is possible that different PH domains have totally different ligand
The 3D structure of several PH domains has been determined . All known
cases have a common structure consisting of two perpendicular anti-parallel
β sheets, followed by a C-terminal amphipathic helix. The loops connecting
the β-strands differ greatly in length, making the PH domain relatively
difficult to detect. There are no totally invariant residues within the PH
Proteins reported to contain one more PH domains belong to the following
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 Act/Rac family, the β-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 yeast CDC24, GTPase activating proteins
like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr.
Cytoskeletal proteins such as dynamin (see <PDOC00362>), Caenorhabditis
elegans kinesin-like protein unc-104 (see <PDOC00343>), spectrin β-
chain, syntrophin (2 PH domains) and yeast nuclear migration protein NUM1.
Mammalian phosphatidylinositol-specific phospholipase C (PI-PLC) (see
<PDOC50007>) isoforms γ and delta. Isoform γ contains two PH
domains, the second one is split into two parts separated by about 400
Oxysterol binding proteins (OSBPs).
Mouse protein citron, a putative rho/rac effector that binds to the GTP-
bound forms of rho and rac,
Several yeast proteins involved in cell cycle regulation and bud formation
like BEM2, BEM3, BUD4 and the BEM1-binding proteins BOI2 (BEB1) and BOI1
Caenorhabditis elegans protein mig-10.
Caenorhabditis elegans hypothetical proteins C04D8.1, K06H7.4 and ZK632.12.
Yeast hypothetical proteins YBR129c and YHR155w.
The profile for the PH domain, which has been developed by Toby Gibson at the
EMBL, covers the total length of domain. Several proteins contain large
insertions in the PH domain and are thus difficult to detect with this
profile. In some of these cases, the profile will align only to one half of
the PH domain.
PROSITE is copyright. It is produced by the SIB Swiss Institute
Bioinformatics. There are no restrictions on its use by non-profit
institutions as long as its content is in no way modified. Usage by and
for commercial entities requires a license agreement. For information
about the licensing scheme send an email to
or see: prosite_license.html.