PROSITE documentation PDOC50003

PH domain profile




Description

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 suggested:

  • 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 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 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 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 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 residues.
  • 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 (BOB1).
  • 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.

Expert(s) to contact by email:

Gibson T.J.

Last update:

March 2002 / Text revised.

Technical section

PROSITE method (with tools and information) covered by this documentation:

PH_DOMAIN, PS50003; PH domain profile  (MATRIX)


References

1AuthorsMayer B.J., Ren R., Clark K.L., Baltimore D.
TitleA putative modular domain present in diverse signaling proteins.
SourceCell 73:629-630(1993).
PubMed ID8500161

2AuthorsHaslam R.J., Koide H.B., Hemmings B.A.
TitlePleckstrin domain homology.
SourceNature 363:309-310(1993).
PubMed ID8497315
DOI10.1038/363309b0

3AuthorsMusacchio A., Gibson T.J., Rice P., Thompson J., Saraste M.
TitleThe PH domain: a common piece in the structural patchwork of signalling proteins.
SourceTrends Biochem. Sci. 18:343-348(1993).
PubMed ID8236453

4AuthorsGibson T.J., Hyvonen M., Musacchio A., Saraste M., Birney E.
TitlePH domain: the first anniversary.
SourceTrends Biochem. Sci. 19:349-353(1994).
PubMed ID7985225

5AuthorsPawson T.
TitleProtein modules and signalling networks.
SourceNature 373:573-580(1995).
PubMed ID7531822
DOI10.1038/373573a0

6AuthorsIngley E., Hemmings B.A.
TitlePleckstrin homology (PH) domains in signal transduction.
SourceJ. Cell. Biochem. 56:436-443(1994).
PubMed ID7890802

7AuthorsSaraste M., Hyvonen M.
TitlePleckstrin homology domains: a fact file.
SourceCurr. Opin. Struct. Biol. 5:403-408(1995).
PubMed ID7583640

8AuthorsRiddihough G.
TitleMore meanders and sandwiches.
SourceNat. Struct. Biol. 1:755-757(1994).
PubMed ID7634082



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