modENCODE |  Help |  blog

Protein Domain : IPR001849

Name  Pleckstrin homology domain Short Name  Pleckstrin_homology
Type  Domain Description  Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. The domains can bind phosphatidylinositol within biological membranes and proteins such as the beta/gamma subunits of heterotrimeric G proteins []and protein kinase C []. Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways.PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.The 3D structure of several PH domains has been determined []. 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 NrkAfamily.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 cerevisiaeCDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr.Cytoskeletal proteins such as dynamin (see ), Caenorhabditis eleganskinesin-like protein unc-104 (see ), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1.Mammalian phosphatidylinositol-specific phospholipase C (PI-PLC) (see ) 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.

Publication Counts Displayer

2 Child Features

DB identifier Name Short Name Type
IPR001605 Pleckstrin homology domain, spectrin-type PH_dom-spectrin-type Domain
IPR024774 Pleckstrin homology domain, Mcp5-type PH_dom-Mcp5-type Domain

0 Contains

3 Cross References

Source . Name

Subject . Primary Identifier
PF00169 PFAM IPR001849
PS50003 PROFILE IPR001849
SM00233 SMART IPR001849

2 Data Sets

Name URL
Swiss-Prot data set
InterPro data set  

10 Found In

DB identifier Name Short Name Type
IPR015727 Protein kinase C mu-related Protein_Kinase_C_mu-related Family
IPR015482 Syntrophin Syntrophin Family
IPR015767 Rho GTPase activating protein Rho_GTPase_act Family
IPR016555 Phospholipase D, eukaryota PLipase_D_euk Family
IPR016279 Phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma PLC-gamma Family
IPR015721 Rho GTP exchange factor RhoGEF-like Family
IPR020684 Rho-associated protein kinase Rho-assoc_coiled-coil_kin Family
IPR015483 Gamma 1 syntrophin Syntrophin_gamma Family
IPR017405 Citron Rho-interacting kinase Citron_Rho-interacting_kinase Family
IPR016609 Uncharacterised conserved protein UCP013217, Opy1p UCP013217_Opy1 Family

0 GO Annotation

0 Ontology Annotations

1 Parent Features

DB identifier Name Short Name Type
IPR011993 Pleckstrin homology-like domain PH_like_dom Domain

1000 Proteins

DB identifier Primary Accession
Organism . Name
FBpp0302018 M9PHU0 Drosophila melanogaster
FBpp0309639 M9PEZ9 Drosophila melanogaster
FBpp0309640 Q9VX48 Drosophila melanogaster
FBpp0302021 E1JJN5 Drosophila melanogaster
FBpp0086123 A1ZAN7 Drosophila melanogaster
FBpp0086124 A1ZAN6 Drosophila melanogaster
FBpp0072194 Q9W1B0 Drosophila melanogaster
FBpp0075035 Q9VVD2 Drosophila melanogaster
FBpp0084350 Q9VBI4 Drosophila melanogaster
FBpp0084351 Q7KRZ3 Drosophila melanogaster
FBpp0089147 Q8IR23 Drosophila melanogaster
FBpp0077948 Q7KTX2 Drosophila melanogaster
FBpp0290817 E1JI59 Drosophila melanogaster
FBpp0290812 E1JJA5 Drosophila melanogaster
FBpp0080123 Q9NGC3 Drosophila melanogaster
FBpp0076096 P48423 Drosophila melanogaster
FBpp0303201 M9PF62 Drosophila melanogaster
FBpp0304983 Q9VZ85 Drosophila melanogaster
FBpp0307725 M9PBE8 Drosophila melanogaster
FBpp0307723 A8DZ19 Drosophila melanogaster
FBpp0111798 A8DZ20 Drosophila melanogaster
FBpp0307724 M9PGB1 Drosophila melanogaster
FBpp0291316 C3KGL5 Drosophila melanogaster
FBpp0080888 Q9VIN1 Drosophila melanogaster
FBpp0305901 M9PHJ6 Drosophila melanogaster
FBpp0074448 Q9NHV9 Drosophila melanogaster
FBpp0112228 A8JUQ9 Drosophila melanogaster
FBpp0083010 Q9VE91 Drosophila melanogaster
FBpp0077947 Q9VP80 Drosophila melanogaster
FBpp0290810 P27619 Drosophila melanogaster