The domain within your query sequence starts at position 472 and ends at position 572; the E-value for the PH domain shown below is 9.56e-11.

LIHEGCLLWKTATGRFKDVLLLLMTDVLVFLQEKDQKYIFTSLDKPSVVSLQNLIVRDIA
NQAKGMFLISSGPPEMYEVHAASRDDRTTWIRVIQQSVRLC

PH

Pleckstrin homology domain.

• SMART accession number: SM00233
• Description: Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. 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.
• Interpro abstract (IPR001849):

  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 [ (PUBMED:8074669) ] and protein kinase C [ (PUBMED:7522330) ]. 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 [ (PUBMED:7634082) ]. 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 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 Saccharomyces 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.
  • C. elegans hypothetical proteins C04D8.1, K06H7.4 and ZK632.12.
  • S. cerevisiae hypothetical proteins YBR129c and YHR155w.

There are 196127 PH domains in 171590 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: signalling
Binding / catalysis: inositol 1, 3, 4, 5-tetrakisphosphate-binding, phosphatidylinositol 4,5-bisphosphate-binding

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Lemmon MA, Ferguson KM
• Pleckstrin homology domains.
• Curr Top Microbiol Immunol. 1998; 228: 39-74

• Carugo KD, Banuelos S, Saraste M
• Crystal structure of a calponin homology domain.
• Nat Struct Biol. 1997; 4: 175-9

The three-dimensional structure of the calponin homology domain present in many actin binding cytoskeletal and signal-transducing proteins has been determined at 2.0 A resolution.

• Fukuda M, Mikoshiba K
• The function of inositol high polyphosphate binding proteins.
• Bioessays. 1997; 19: 593-603

The inositol phosphate metabolism network has been found to be much more complex than previously thought, as more and more inositol phosphates and their metabolizing enzymes have been discovered. Some of the inositol phosphates have been shown to have biological activities, but little is known about their signal transduction mechanisms except for that of inositol 1,4,5-trisphosphate. The recent discovery, however, of a number of binding proteins for inositol high polyphosphate [inositol 1,3,4,5-tetrakisphosphate (IP4), inositol 1,3,4,5,6-pentakisphosphate, or inositol hexakisphosphate] enables us to speculate on the physiological function of these compounds. In this article we focus on two major issues: (1) the roles of inositol high polyphosphates in vesicular trafficking, especially exocytosis, and (2) pleckstrin homology domain-containing IP4 binding proteins involved in the Ras signaling pathway.

• Hyvonen M, Saraste M
• Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia.
• EMBO J. 1997; 16: 3396-404

Bruton's tyrosine kinase (Btk) is an enzyme which is involved in maturation of B cells. It is a target for mutations causing X-linked agammaglobulinaemia (XLA) in man. We have determined the structure of the N-terminal part of Btk by X-ray crystallography at 1.6 A resolution. This part of the kinase contains a pleckstrin homology (PH) domain and a Btk motif. The structure of the PH domain is similar to those published previously: a seven-stranded bent beta-sheet with a C-terminal alpha-helix. Individual point mutations within the Btk PH domain which cause XLA can be classified as either structural or functional in the light of the three-dimensional structure and biochemical data. All functional mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids. It is likely that these mutations inactivate the Btk pathway in cell signalling by reducing its affinity for inositol phosphates, which causes a failure in translocation of the kinase to the cell membrane. A small number of signalling proteins contain a Btk motif that always follows a PH domain in the sequence. This small module has a novel fold which is held together by a zinc ion bound by three conserved cysteines and a histidine. The Btk motif packs against the second half of the beta-sheet of the PH domain, forming a close contact with it. Our structure opens up new ways to study the role of the PH domain and Btk motif in the cellular function of Btk and the molecular basis of its dysfunction in XLA patients.

• Muhlberg AB, Warnock DE, Schmid SL
• Domain structure and intramolecular regulation of dynamin GTPase.
• EMBO J. 1997; 16: 6676-83

Dynamin is a 100 kDa GTPase required for receptor-mediated endocytosis, functioning as the key regulator of the late stages of clathrin-coated vesicle budding. It is specifically targeted to clathrin-coated pits where it self-assembles into 'collars' required for detachment of coated vesicles from the plasma membrane. Self-assembly stimulates dynamin GTPase activity. Thus, dynamin-dynamin interactions are critical in regulating its cellular function. We show by crosslinking and analytical ultracentrifugation that dynamin is a tetramer. Using limited proteolysis, we have defined structural domains of dynamin and evaluated the domain interactions and requirements for self-assembly and GTP binding and hydrolysis. We show that dynamin's C-terminal proline- and arginine-rich domain (PRD) and dynamin's pleckstrin homology (PH) domain are, respectively, positive and negative regulators of self-assembly and GTP hydrolysis. Importantly, we have discovered that the alpha-helical domain interposed between the PH domain and the PRD interacts with the N-terminal GTPase domain to stimulate GTP hydrolysis. We term this region the GTPase effector domain (GED) of dynamin.

• Tanaka K et al.
• A target of phosphatidylinositol 3,4,5-trisphosphate with a zinc finger motif similar to that of the ADP-ribosylation-factor GTPase-activating protein and two pleckstrin homology domains.
• Eur J Biochem. 1997; 245: 512-9

We have purified a protein that binds phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] using beads bearing a PtdIns(3,4,5)P3 analogue. This protein, with a molecular mass of 43 kDa, was termed PtdIns(3,4,5)P3-binding protein. The partial amino acid sequences were determined and a full-length cDNA encoding the protein was isolated from bovine brain cDNA library. The clone harbored an open reading frame of 373 amino acids which contained one zinc finger motif similar to that of ADP-ribosylation-factor GTPase-activating protein and two pleckstrin homology domains. The entire sequence was 83% similar to centaurin alpha, another PtdIns(3,4,5)P3-binding protein. The protein bound PtdIns(3,4,5)P3 with a higher affinity than it did inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4-bisphosphate, and phosphatidylinositol 3-phosphate suggesting that the binding to PtdIns(3,4,5)P3 was specific. The binding activity was weaker in the mutants with a point mutation in the conserved sequences in each pleckstrin homology domain. Introduction of both mutations abolished the activity. These results suggest that this new binding protein binds PtdIns(3,4,5)P3 through two pleckstrin domains present in the molecule.

• Perez-Alvarado GC, Kosa JL, Louis HA, Beckerle MC, Winge DR, Summers MF
• Structure of the cysteine-rich intestinal protein, CRIP.
• J Mol Biol. 1996; 257: 153-74

LIM domains are Zn-binding arrays found in a number of proteins involved in the control of cell differentiation, including several developmentally regulated transcription factors and a human proto-oncogene product. The rat cysteine-rich intestinal protein, CRIP, is a 76-residue polypeptide which contains a LIM motif. The solution structure of CRIP has been determined by homonuclear and 1H-15N heteronuclear correlated nuclear magnetic resonance spectroscopy. Structures with individual distance violations of < or = 0.03 angstrom and penalties (squared sum of distance violations) of < or = 0.06 angstrom2 were generated with a total of 500 nuclear Overhauser effect (NOE)-derived distance restraints (averaging 15.6 restraints per refined residue). Superposition of backbone heavy atoms of ordered residues relative to mean atom positions is achieved with pairwise rms deviations of 0.54(+/-0.14) angstrom. As observed previously for a peptide with the sequence of the C-terminal LIM domain from the avian cysteine-rich protein, CRP (cCRP-LIM2), CRIP binds two equivalents of zinc, forming N-terminal CCHC (Cys3, Cys6, His24, Cys27) and C-terminal CCCC (Cys30, Cys33, Cys51, Cys55) modules. The CCHC and CCCC modules in CRIP contain two orthogonally-arrayed antiparallel beta-sheets. The C-terminal end of the CCHC module contains a tight turn and the C terminus of the CCCC module forms an alpha-helix. The modules pack via hydrophobic interactions, forming a compact structure that is similar to that observed for cCRP-LIM2. The most significant differences between the structures occur at the CCHC module-CCCC module interface, which results in a difference in the relative orientations of the modules, and at the C terminus where the alpha-helix appears to be packed more tightly against the preceding antiparallel beta-sheet. The greater abundance of NOE information obtained for CRIP relative to cCRP-LIM2, combined with the analysis of J-coupling and proton chemical shift data, have allowed a more detailed evaluation of the molecular level interactions that stabilize the fold of the LIM motif.

• Ponting CP, Bork P
• Pleckstrin's repeat performance: a novel domain in G-protein signaling?
• Trends Biochem Sci. 1996; 21: 245-6

• Sakane F, Imai S, Kai M, Wada I, Kanoh H
• Molecular cloning of a novel diacylglycerol kinase isozyme with a pleckstrin homology domain and a C-terminal tail similar to those of the EPH family of protein-tyrosine kinases.
• J Biol Chem. 1996; 271: 8394-401

A fourth member of the diacylglycerol kinase (DGK) gene family termed DGK delta was cloned from the human testis cDNA library. The cDNA sequence contains an open reading frame of 3,507 nucleotides encoding a putative DGK protein of 130,006 Da. Interestingly, the new DGK isozyme contains a pleckstrin homology domain found in a number of proteins involved in signal transduction. Furthermore, the C-terminal tail of this isozyme is very similar to those of the EPH family of receptor tyrosine kinases. The primary structure of the delta-isozyme also has two cysteine-rich zinc finger-like structures (C3 region) and the C-terminal C4 region, both of which have been commonly found in the three isozymes previously cloned (DGKs alpha, beta and gamma). However, DGK delta lacks the EF-hand motifs (C2) and contains a long Glu- and Ser-rich insertion (317 residues), which divides the C4 region into two portions. Taken together, these structural features of DGK delta indicate that this isozyme belongs to a DGK subfamily distinct from that consisting of DGKs alpha, beta, and gamma. Increased DGK activity without marked preference to arachidonoyl type of diacylglycerol was detected in the particulate fraction of COS-7 cells expressing the transfected DGKdelta cDNA. The enzyme activity was independent of phosphatidylserine, which is a common activator for the previously sequenced DGKs. Northern blot analysis showed that the DGK delta mRNA (approximately 6.3 kilobases) is most abundant in human skeletal muscle but undetectable in the brain, thymus, and retina. This expression pattern is different from those of the previously cloned DGKs. Our results show that the DGK gene family consists of at least two subfamilies consisting of enzymes with distinct structural characteristics and that each cell type probably expresses its own characteristic repertoire of DGKs whose functions may be regulated through different signal transduction pathways.

• Shaw G
• The pleckstrin homology domain: an intriguing multifunctional protein module.
• Bioessays. 1996; 18: 35-46

Pleckstrin homology (PH) domains are a family of compact protein modules defined by sequences of roughly 100 amino acids. These domains are common in vertebrate, Drosophila, C. elegans and yeast proteins, suggesting an early origin and fundamental importance to eukaryotic biology. Many enzymes which have important regulatory functions contain PH domains, and mutant forms of several such proteins are implicated in oncogenesis and developmental disorders. Numerous recent studies show that PH domains bind various proteins and inositolphosphates. Here I discuss PH domains in detail and conclude that they form a versatile family of membrane binding and protein localization modules.

• Thornton KH, Mueller WT, McConnell P, Zhu G, Saltiel AR, Thanabal V
• Nuclear magnetic resonance solution structure of the growth factor receptor-bound protein 2 Src homology 2 domain.
• Biochemistry. 1996; 35: 11852-64

A family of NMR solution structures of the growth factor receptor-bound protein 2 (Grb2) SH2 domain has been determined by heteronuclear multidimensional NMR. Proton, nitrogen, and carbon chemical shift assignments have been made for the SH2 domain of Grb2. Assignments were made from a combination of homonuclear two-dimensional and 15N- and 13C-edited three-dimensional spectra at pH 6.2 and 298 K. Structure-induced proton and carbon secondary shifts were calculated and used to facilitate the spectral assignment process. NOE, scalar coupling, secondary chemical shift, and amide proton exchange data were used to characterize the secondary structural elements and hydrogen-bonding network in the Grb2 SH2 domain. The three-dimensional structure of the Grb2 SH2 domain was calculated using 1112 restraints obtained from NOE, coupling constant, and amide proton exchange data. The rmsd for the 24 calculated structures to the mean structure of the Grb2 SH2 domain was 0.75 A for backbone and 1.28 A for all heavy atoms. The three-dimensional fold of the Grb2 SH2 domain is similar to that observed for other SH2 domains and consists of two alpha-helical segments and eight beta-strands, six strands that make up two contiguous antiparallel beta-sheets, and two strands that form two short parallel beta-sheets. The structure of the phosphotyrosine binding pocket of Grb2 is similar to that observed for other SH2 domains. The hydrophobic binding pocket of Grb2 is similar to that observed for Src with the exception that tryptophan 121 of Grb2 occupies part of the pY+3 binding pocket. Structural implications for the Grb2 SH2 domain selectivity at the pY+2 and pY+3 sites are discussed.

• Ferguson KM, Lemmon MA, Schlessinger J, Sigler PB
• Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain.
• Cell. 1995; 83: 1037-46

The X-ray crystal structure of the high affinity complex between the pleckstrin homology (PH) domain from rat phospholipase C-delta 1 (PLC-delta 1) and inositol-(1,4,5)-trisphosphate (Ins(1,4,5)P3) has been refined to 1.9 A resolution. The domain fold is similar to others of known structure. Ins(1,4,5)P3 binds on the positively charged face of the electrostatically polarized domain, interacting predominantly with the beta 1/beta 2 and beta 3/beta 4 loops. The 4- and 5-phosphate groups of Ins(1,4,5)P3 interact much more extensively than the 1-phosphate. Two amino acids in the PLC-delta 1 PH domain that contact Ins(1,4,5)P3 have counterparts in the Bruton's tyrosine kinase (Btk) PH domain, where mutational changes cause inherited agammaglobulinemia, suggesting a mechanism for loss of function in Btk mutants. Using electrostatics and varying levels of head-group specificity, PH domains may localize and orient signaling proteins, providing a general membrane targeting and regulatory function.

• Fushman D, Cahill S, Lemmon MA, Schlessinger J, Cowburn D
• Solution structure of pleckstrin homology domain of dynamin by heteronuclear NMR spectroscopy.
• Proc Natl Acad Sci U S A. 1995; 92: 816-20

The pleckstrin homology (PH) domain is a recognition motif thought to be involved in signal-transduction pathways controlled by a variety of cytoplasmic proteins. Assignments of nearly all 1H, 13C, and 15N resonances of the PH domain from dynamin have been obtained from homonuclear and heteronuclear NMR experiments. The secondary structure has been elucidated from the pattern of nuclear Overhauser enhancements, from 13C chemical shift deviations, and from observation of slowly exchanging amide hydrogens. The secondary structure contains one alpha-helix and eight beta-strands, seven of which are arranged in two contiguous, antiparallel beta-sheets. The structure is monomeric, in contrast to the well-defined intimate dimerization of the crystal structure of this molecule. Residues possibly involved in ligand binding are in apparently flexible loops. Steady-state 15N(1H) nuclear Overhauser effect measurements indicate unequivocally the boundaries of this PH domain, and the structured portion of the domain appears to be more extended to the C terminus than previously suggested for other PH domains.

• Hyvonen M, Macias MJ, Nilges M, Oschkinat H, Saraste M, Wilmanns M
• Structure of the binding site for inositol phosphates in a PH domain.
• EMBO J. 1995; 14: 4676-85

Phosphatidylinositol bisphosphate has been found to bind specifically to pleckstrin homology (PH) domains that are commonly present in signalling proteins but also found in cytoskeleton. We have studied the complexes of the beta-spectrin PH domain and soluble inositol phosphates using both circular dichroism and nuclear magnetic resonance spectroscopy, and X-ray crystallography. The specific binding site is located in the centre of a positively charged surface patch of the domain. The presence of 4,5-bisphosphate group on the inositol ring is critical for binding. In the crystal structure that has been determined at 2.0 A resolution, inositol-1,4,5-trisphosphate is bound with salt bridges and hydrogen bonds through these phosphate groups whereas the 1-phosphate group is mostly solvent-exposed and the inositol ring has virtually no interactions with the protein. We propose a model in which PH domains are involved in reversible anchoring of proteins to membranes via their specific binding to phosphoinositides. They could also participate in a response to a second messenger such as inositol trisphosphate, organizing cross-roads in cellular signalling.

• Ponting CP
• SAM: a novel motif in yeast sterile and Drosophila polyhomeotic proteins.
• Protein Sci. 1995; 4: 1928-30

Single copies of an approximately 65-70 residue domain are shown to be present in the sequences of 14 eukaryotic proteins, including yeast byr2, STE11, ste4, and STE50, which are essential participants in sexual differentiation. This domain, named SAM (sterile alpha motif), appears to participate in other developmental processes because it is also present in Drosophila polyhomeotic gene product and related homologues, which are thought to regulate determination of segmental specification in early embryogenesis. Its appearance in byr2 and STE11, which are MEK kinases, and in proteins containing pleckstrain homology, src homology 3, and discs-large homologous region domains, suggests possible participation in signal transduction pathways.

• Xiao B et al.
• Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways.
• Nature. 1995; 376: 188-91

A broad range of organisms and tissues contain 14-3-3 proteins, which have been associated with many diverse functions including critical roles in signal transduction pathways, exocytosis and cell cycle regulation. We report here the crystal structure of the human T-cell 14-3-3 isoform (tau) dimer at 2.6 A resolution. Each monomer (Mr 28K) is composed of an unusual arrangement of nine antiparallel alpha-helices organized as two structural domains. The dimer creates a large, negatively charged channel approximately 35 A broad, 35 A wide and 20 A deep. Overall, invariant residues line the interior of this channel whereas the more variable residues are distributed on the outer surface. At the base of this channel is a 16-residue segment of 14-3-3 which has been implicated in the binding of 14-3-3 to protein kinase C.

• Zhang P, Talluri S, Deng H, Branton D, Wagner G
• Solution structure of the pleckstrin homology domain of Drosophila beta-spectrin.
• Structure. 1995; 3: 1185-95

BACKGROUND: The pleckstrin homology (PH) domain, which is approximately 100 amino acids long, has been found in about 70 proteins involved in signal transduction and cytoskeletal function, a frequency comparable to SH2 (src homology 2) and SH3 domains. PH domains have been shown to bind the beta gamma-subunits of G-proteins and phosphatidylinositol 4,5-bisphosphate (PIP2). It is conceivable that the PH domain of beta-spectrin plays a part in the association of spectrin with the plasma membrane of cells. RESULTS: We have solved the solution structure of the 122-residue PH domain of Drosophila beta-spectrin. The overall fold consists of two antiparallel beta-sheets packing against each other at an angle of approximately 60 degrees to form a beta-sandwich, a two-turn alpha-helix unique to spectrin PH domains, and a four-turn C-terminal alpha-helix. One of the major insertions in beta-spectrin PH domains forms a long, basic surface loop and appears to undergo slow conformational exchange in solution. This loop shows big spectral changes upon addition of D-myo-inositol 1,4,5-trisphosphate (IP3). CONCLUSIONS: We propose that the groove at the outer surface of the second beta-sheet is an important site of association with other proteins. This site and the possible lipid-binding site can serve to localize the spectrin network under the plasma membrane. More generally, it has to be considered that the common fold observed for the PH domain structures solved so far does not necessarily mean that all PH domains have similar functions. In fact, the residues constituting potential binding sites for ligands or other proteins are only slightly conserved between different PH domains.

• Zhou MM et al.
• Structure and ligand recognition of the phosphotyrosine binding domain of Shc.
• Nature. 1995; 378: 584-92

The nuclear magnetic resonance structure of the phosphotyrosine binding (PTB) domain of Shc complexed to a phosphopeptide reveals an alternative means of recognizing tyrosine-phosphorylated proteins. Unlike in SH2 domains, the phosphopeptide forms an antiparallel beta-strand with a beta-sheet of the protein, interacts with a hydrophobic pocket through the (pY-5) residue, and adopts a beta-turn. The PTB domain is structurally similar to pleckstrin homology domains (a beta-sandwich capped by an alpha-helix) and binds to acidic phospholipids, suggesting a possible role in membrane localization.

• Downing AK, Driscoll PC, Gout I, Salim K, Zvelebil MJ, Waterfield MD
• Three-dimensional solution structure of the pleckstrin homology domain from dynamin.
• Curr Biol. 1994; 4: 884-91

BACKGROUND: The pleckstrin homology (PH) domain is a region of approximately 100 amino acids, defined by sequence similarity, that has been found in about 60 proteins, many of which are involved in signal transduction downstream of cell surface receptors; the function of PH domains is unknown. The only clue to the function of PH domains is the circumstantial evidence that they may link beta gamma subunits of G proteins to second messenger systems. Knowledge of the three-dimensional structures of PH domains should help to elucidate the roles they play in the proteins that contain them. RESULTS: Using homonuclear and heteronuclear magnetic resonance spectroscopy, we have determined the solution structure of the PH domain of the GTPase dynamin, one of a number of proteins that have PH domains and interact with GTP. The fold of the dynamin PH domain is composed of two antiparallel beta-sheets, which pack face-to-face at an angle of approximately 60 degrees. The first beta-sheet comprises four strands (residues 13-58) from the amino-terminal half of the protein sequence; the second beta-sheet contains three strands (residues 63-99). A single alpha-helix (residues 102-116) flanks one edge of the interface between the two sheets, parallel in orientation to the second sheet, in an alpha/beta roll motif similar to that of the B oligomer of verotoxin-1 from Escherichia coli. CONCLUSIONS: The structure of the dynamin PH domain is very similar to the recently reported structures of the pleckstrin and spectrin PH domains. This shows that, despite the low level of sequence similarity between different PH domains, they do have a characteristic polypeptide fold. On the basis of our structure, the suggestion that PH domains engage in coiled-coil interactions with G protein beta gamma subunits seems unlikely and should be re-evaluated.

• Ferguson KM, Lemmon MA, Schlessinger J, Sigler PB
• Crystal structure at 2.2 A resolution of the pleckstrin homology domain from human dynamin.
• Cell. 1994; 79: 199-209

The X-ray crystal structure of the pleckstrin homology (PH) domain from human dynamin has been refined to 2.2 A resolution. A seven-stranded beta sandwich of two orthogonal antiparallel beta sheets is closed at one corner by a C-terminal alpha helix. Opposite this helix are the three loops that vary most among PH domains. The basic fold is very similar to that of two other PH domains recently determined by nuclear magnetic resonance, confirming that PH domain with known structure is electrostatically polarized, with the three variable loops forming a positively charged surface. This surface includes the position of the X-linked immunodeficiency mutation in the Btk PH domain and may serve as a ligand-binding surface.

• Gibson TJ, Hyvonen M, Musacchio A, Saraste M, Birney E
• PH domain: the first anniversary.
• Trends Biochem Sci. 1994; 19: 349-53

• Harlan JE, Hajduk PJ, Yoon HS, Fesik SW
• Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate.
• Nature. 1994; 371: 168-70

The pleckstrin homology (PH) domain is a new protein module of around 100 amino acids found in several proteins involved in signal transduction. Although its specific function has yet to be elucidated, the carboxy-terminal regions of many PH domains bind to the beta gamma subunits of G proteins. On the basis of structural similarities between PH domains and lipid-binding proteins, we have proposed that PH domains may be binding to lipophilic molecules. Indeed, many of the proteins that contain this domain associate with phospholipid membranes, and disruption of this domain can interfere with membrane association. Here we report that PH domains bind to phosphatidylinositol-4,5-bisphosphate and show that the lipid-binding site is located at the lip of the beta-barrel. This suggests that PH domains may be important for membrane localization of proteins through interactions with phosphatidylinositol-4,5-bisphosphate.

• Macias MJ, Musacchio A, Ponstingl H, Nilges M, Saraste M, Oschkinat H
• Structure of the pleckstrin homology domain from beta-spectrin.
• Nature. 1994; 369: 675-7

The 'pleckstrin homology' or PH domain is a 100-residue protein module. It is present in many kinases, different isoforms of phospholipase C, GTPase-activating proteins and nucleotide-exchange factors. Its function is not known, but many proteins that contain a PH domain interact with GTP-binding proteins. The PH domain in beta-adrenergic receptor kinase may be involved in binding to the beta gamma subunits of a trimeric G-protein. We report here the three-dimensional structure of the PH domain of the cytoskeletal protein spectrin using homonuclear nuclear magnetic resonance. The core of the molecule is an antiparallel beta-sheet consisting of seven strands. The C terminus is folded into a long alpha-helix, and another helix is present in one of the surface loops. The molecule is electrostatically polarized and contains a pocket which may be involved in the binding of a ligand. There is a distant relationship to the peptidyl-prolyl-cis-trans-isomerase FKBP in which this pocket is involved in the binding of the macrocyclic compound FK506 (refs 8-11).

• Timm D, Salim K, Gout I, Guruprasad L, Waterfield M, Blundell T
• Crystal structure of the pleckstrin homology domain from dynamin.
• Nat Struct Biol. 1994; 1: 782-8

The pleckstrin homology (PH) domain is a conserved module present in many signal transducing and cytoskeletal proteins. Here we report the 2.8 A crystal structure of the PH domain from dynamin. This domain consists of seven beta-strands forming two roughly orthogonal antiparallel beta-sheets terminating with an amphipathic alpha-helix. The structure also reveals a non-covalent dimeric association of the PH domain and a hydrophobic pocket surrounded by a charged rim. The dynamin PH domain structure is discussed in relation to its potential role in mediating interactions between proteins.

• Vihinen M, Nilsson L, Smith CI
• Tec homology (TH) adjacent to the PH domain.
• FEBS Lett. 1994; 350: 263-5

The pleckstrin homology (PH) domain is extended in the Btk kinase family by a region designated the TH (Tec homology) domain, which consists of about 80 residues preceding the SH3 domain. The TH domain contains a conserved 27 amino acid stretch designated the Btk motif and a proline-rich region. Sequence similarity was found to a putative Ras GTPase activating protein and a human interferon-gamma binding protein both in the PH domain and the Btk motif region. SLK1/SSP31 protein kinase and a non-catalytic p85 subunit of PI-3 kinase had similarity only with the proline rich region. The identification of a PH domain extension in some signal transduction proteins in different species suggests that this region is involved in protein-protein interactions.

• Yoon HS, Hajduk PJ, Petros AM, Olejniczak ET, Meadows RP, Fesik SW
• Solution structure of a pleckstrin-homology domain.
• Nature. 1994; 369: 672-5

Pleckstrin, the major protein kinase C substrate of platelets, contains domains of about 100 amino acids at the amino and carboxy termini that have been found in a number of proteins, including serine/threonine kinases, GTPase-activating proteins, phospholipases and cytoskeletal proteins. These conserved sequences, termed pleckstrin-homology (PH) domains, are thought to be involved in signal transduction. But the details of the function and binding partners of the PH domains have not been characterized. Here we report the solution structure of the N-terminal pleckstrin-homology domain of pleckstrin determined using heteronuclear three-dimensional nuclear magnetic resonance spectroscopy. The structure consists of an up-and-down beta-barrel of seven antiparallel beta-strands and a C-terminal amphiphilic alpha-helix that caps one end of the barrel. The overall topology of the domain is similar to that of the retinol-binding protein family of structures.

• Haslam RJ, Koide HB, Hemmings BA
• Pleckstrin domain homology.
• Nature. 1993; 363: 309-10

• Kohda D et al.
• Solution structure of the SH3 domain of phospholipase C-gamma.
• Cell. 1993; 72: 953-60

SH3 (Src homology 3) domains are found in many signaling proteins and appear to function as binding modules for cytoplasmic target proteins. The solution structure of the SH3 domain of human phospholipase C-gamma (PLC-gamma) was determined by two-dimensional 1H NMR analysis. This SH3 domain is composed of eight antiparallel beta strands consisting of two successive "Greek key" motifs, which form a barrel-like structure. The conserved aliphatic and aromatic residues form a hydrophobic pocket on the molecular surface, and the conserved carboxylic residues are localized to the periphery. The hydrophobic pocket may serve as a binding site for target proteins. Analysis of the slowly exchanging amide protons by NMR measurements indicates that despite containing a high content of beta structure, the SH3 domain of PLC-gamma is flexible.

• Mayer BJ, Ren R, Clark KL, Baltimore D
• A putative modular domain present in diverse signaling proteins.
• Cell. 1993; 73: 629-30

• Musacchio A, Gibson T, Rice P, Thompson J, Saraste M
• The PH domain: a common piece in the structural patchwork of signalling proteins.
• Trends Biochem Sci. 1993; 18: 343-8

The 'pleckstrin homology' domain is an approximately 100-residue protein module that has recently been added to the domain catalogue of signalling proteins. For this review we have made an extensive database search using a profile search method, and found a number of additional proteins that may contain PH domains. The PH domain is present in many kinases, isoforms of phospholipase C, GTPases, GTPase-activating proteins and nucleotide-exchange factors, including such proteins as Vav, Dbl and Bcr, and there are two PH domains in a guanine-nucleotide releasing factor of Ras. Many PH-domain-containing proteins interact with GTP-binding proteins. We have also identified a PH domain in beta-adrenergic receptor kinase exactly in the region that has already been shown to be involved in binding to the beta and gamma subunits of a heterotrimeric G protein. This suggests that PH domains may be involved in interactions with GTP-binding proteins.

• Musacchio A, Noble M, Pauptit R, Wierenga R, Saraste M
• Crystal structure of a Src-homology 3 (SH3) domain.
• Nature. 1992; 359: 851-5

The Src-homologous SH3 domain is a small domain present in a large number of proteins that are involved in signal transduction, such as the Src protein tyrosine kinase, or in membrane-cytoskeleton interactions, but the function of SH3 is still unknown (reviewed in refs 1-3). Here we report the three-dimensional structure at 1.8 A resolution of the SH3 domain of the cytoskeletal protein spectrin expressed in Escherichia coli. The domain is a compact beta-barrel made of five antiparallel beta-strands. The amino acids that are conserved in the SH3 sequences are located close to each other on one side of the molecule. This surface is rich in aromatic and carboxylic amino acids, and is distal to the region of the molecule where the N and C termini reside and where SH3 inserts into the alpha-spectrin chain. We suggest that a protein ligand binds to this conserved surface of SH3.

Disease (disease genes where sequence variants are found in this domain)

SwissProt sequences and OMIM curated human diseases associated with missense mutations within the PH domain.

Protein	Disease
Tyrosine-protein kinase BTK (Q06187) (SMART)	OMIM:300300: Agammaglobulinemia, type 1, X-linked ; ?XLA and isolated growth hormone deficiency OMIM:307200:

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
6.15	map04810	Regulation of actin cytoskeleton
4.81	map04664	Fc epsilon RI signaling pathway
4.70	map04510	Focal adhesion
4.14	map04660	T cell receptor signaling pathway
3.69	map04010	MAPK signaling pathway
3.69	map04012	ErbB signaling pathway
3.58	map04910	Insulin signaling pathway
3.24	map05223	Non-small cell lung cancer
3.13	map04670	Leukocyte transendothelial migration
3.13	map04650	Natural killer cell mediated cytotoxicity
3.07	map05214	Glioma
2.96	map05220	Chronic myeloid leukemia
2.85	map05211	Renal cell carcinoma
2.68	map04662	B cell receptor signaling pathway
2.52	map05210	Colorectal cancer
2.40	map05213	Endometrial cancer
2.40	map04070	Phosphatidylinositol signaling system
2.40	map05215	Prostate cancer
2.24	map04630	Jak-STAT signaling pathway
2.24	map04360	Axon guidance
2.24	map05221	Acute myeloid leukemia
2.18	map04370	VEGF signaling pathway
2.12	map04920	Adipocytokine signaling pathway
2.07	map00562	Inositol phosphate metabolism
2.01	map05212	Pancreatic cancer
1.96	map04912	GnRH signaling pathway
1.90	map04020	Calcium signaling pathway
1.51	map04150	mTOR signaling pathway
1.45	map00564	Glycerophospholipid metabolism
1.34	map05222	Small cell lung cancer
1.34	map04530	Tight junction
1.34	map04620	Toll-like receptor signaling pathway
1.34	map04210	Apoptosis
1.34	map05218	Melanoma
1.34	map04914	Progesterone-mediated oocyte maturation
1.06	map00565	Ether lipid metabolism
0.95	map05120	Epithelial cell signaling in Helicobacter pylori infection
0.89	map04310	Wnt signaling pathway
0.89	map04350	TGF-beta signaling pathway
0.89	map04320	Dorso-ventral axis formation
0.89	map04540	Gap junction
0.78	map04930	Type II diabetes mellitus
0.67	map05040	Huntington's disease
0.39	map00561	Glycerolipid metabolism
0.34	map04520	Adherens junction
0.34	map05030	Amyotrophic lateral sclerosis (ALS)
0.17	map03320	PPAR signaling pathway
0.11	map00600	Sphingolipid metabolism
0.06	map00632	Benzoate degradation via CoA ligation
0.06	map04610	Complement and coagulation cascades

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PH domain which could be assigned to a KEGG orthologous group, and not all proteins containing PH domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of PH domains in PDB

PDB code	Title
1awe	HUMAN SOS1 PLECKSTRIN HOMOLOGY (PH) DOMAIN, NMR, 20 STRUCTURES
1b55	PH DOMAIN FROM BRUTON'S TYROSINE KINASE IN COMPLEX WITH INOSITOL 1,3,4,5-TETRAKISPHOSPHATE
1bak	SIGNAL TRANSDUCTION PLECKSTRIN HOMOLOGY DOMAIN OF G-PROTEIN COUPLED RECEPTOR KINASE 2 (BETA-ADRENERGIC RECEPTOR KINASE 1), C-TERMINAL EXTENDED, NMR, 20 STRUCTURES
1btk	PH DOMAIN AND BTK MOTIF FROM BRUTON'S TYROSINE KINASE MUTANT R28C
1btn	STRUCTURE OF THE BINDING SITE FOR INOSITOL PHOSPHATES IN A PH DOMAIN
1bwn	PH DOMAIN AND BTK MOTIF FROM BRUTON'S TYROSINE KINASE MUTANT E41K IN COMPLEX WITH INS(1,3,4,5)P4
1dbh	DBL AND PLECKSTRIN HOMOLOGY DOMAINS FROM HSOS1
1dro	NMR STRUCTURE OF THE CYTOSKELETON/SIGNAL TRANSDUCTION PROTEIN
1dyn	CRYSTAL STRUCTURE AT 2.2 ANGSTROMS RESOLUTION OF THE PLECKSTRIN HOMOLOGY DOMAIN FROM HUMAN DYNAMIN
1eaz	Crystal structure of the phosphoinositol (3,4)-bisphosphate binding PH domain of TAPP1 from human.
1fao	STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN FROM DAPP1/PHISH IN COMPLEX WITH INOSITOL 1,3,4,5-TETRAKISPHOSPHATE
1fb8	STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN FROM DAPP1/PHISH
1fgy	GRP1 PH DOMAIN WITH INS(1,3,4,5)P4
1fgz	GRP1 PH DOMAIN (UNLIGANDED)
1fho	Solution Structure of the PH Domain from the C. Elegans Muscle Protein UNC-89
1fhw	Structure of the pleckstrin homology domain from GRP1 in complex with inositol(1,3,4,5,6)pentakisphosphate
1fhx	Structure of the pleckstrin homology domain from GRP1 in complex with inositol 1,3,4,5-tetrakisphosphate
1foe	CRYSTAL STRUCTURE OF RAC1 IN COMPLEX WITH THE GUANINE NUCLEOTIDE EXCHANGE REGION OF TIAM1
1h10	HIGH RESOLUTION STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PROTEIN KINASE B/AKT BOUND TO INS(1,3,4,5)-TETRAKISPHOPHATE
1ki1	Guanine Nucleotide Exchange Region of Intersectin in Complex with Cdc42
1kz7	Crystal Structure of the DH/PH Fragment of Murine Dbs in Complex with the Placental Isoform of Human Cdc42
1kzg	DbsCdc42(Y889F)
1lb1	Crystal Structure of the Dbl and Pleckstrin homology domains of Dbs in complex with RhoA
1mai	STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN FROM PHOSPHOLIPASE C DELTA IN COMPLEX WITH INOSITOL TRISPHOSPHATE
1mph	PLECKSTRIN HOMOLOGY DOMAIN FROM MOUSE BETA-SPECTRIN, NMR, 50 STRUCTURES
1nty	Crystal structure of the first DH/PH domain of Trio to 1.7 A
1omw	Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and gamma 2 subunits
1p6s	Solution Structure of the Pleckstrin Homology Domain of Human Protein Kinase B beta (Pkb/Akt)
1pls	SOLUTION STRUCTURE OF A PLECKSTRIN HOMOLOGY DOMAIN
1pms	PLECKSTRIN HOMOLOGY DOMAIN OF SON OF SEVENLESS 1 (SOS1) WITH GLYCINE-SERINE ADDED TO THE N-TERMINUS, NMR, 20 STRUCTURES
1qqg	CRYSTAL STRUCTURE OF THE PH-PTB TARGETING REGION OF IRS-1
1rj2	Crystal structure of the DH/PH fragment of Dbs without bound GTPase
1txd	Crystal Structure of the DH/PH domains of Leukemia-associated RhoGEF
1u27	Triglycine variant of the ARNO Pleckstrin Homology Domain in complex with Ins(1,3,4,5)P4
1u29	Triglycine variant of the ARNO Pleckstrin Homology Domain in complex with Ins(1,4,5)P3
1u2b	Triglycine variant of the Grp1 Pleckstrin Homology Domain unliganded
1u5d	Crystal Structure of the PH domain of SKAP55
1u5e	Crystal Structure of a N-terminal Fragment of SKAP-Hom Containing Both the Helical Dimerization Domain and the PH Domain
1u5f	Crystal Structure of the PH Domain of SKAP-Hom with 8 Vector-derived N-terminal Residues
1u5g	Crystal Structure of the PH Domain of SKAP-Hom
1unp	Crystal structure of the pleckstrin homology domain of PKB alpha
1unq	High resolution crystal structure of the Pleckstrin Homology Domain Of Protein Kinase B/Akt Bound To Ins(1,3,4,5)-Tetrakisphophate
1unr	Crystal structure of the PH domain of PKB alpha in complex with a sulfate molecule
1upq	Crystal structure of the pleckstrin homology (PH) domain of PEPP1
1upr	Crystal structure of the PEPP1 pleckstrin homology domain in complex with Inositol 1,3,4,5-tetrakisphosphate
1v5m	Solution Structure of the Pleckstrin Homology Domain of Mouse APS
1v5p	Solution Structure of the N-terminal Pleckstrin Homology Domain Of TAPP2 from Mouse
1v5u	Solution Structure of the C-terminal Pleckstrin Homology Domain of Sbf1 from Mouse
1v61	Solution Structure of the Pleckstrin Homology Domain of alpha-Pix
1v88	Solution Structure of the Pleckstrin Homology Domain of Oxysterol-Binding Protein-Related Protein 8 (KIAA1451 Protein)
1v89	Solution Structure of the Pleckstrin Homology Domain of Human KIAA0053 Protein
1wg7	Solution structure of pleckstrin homology domain from human KIAA1058 protein
1wgq	Solution Structure of the Pleckstrin Homology Domain of Mouse Ethanol Decreased 4 Protein
1wi1	Solution structure of the PH domain of human calcium-dependent activator protein for secretion (CAPS)
1wjm	Solution structure of pleckstrin homology domain of human beta III spectrin.
1x05	Solution structure of the C-terminal PH domain of human pleckstrin
1x1f	Solution structure of the PH domain of human Docking protein BRDG1
1x1g	Solution structure of the C-terminal PH domain of human pleckstrin 2
1x86	Crystal Structure of the DH/PH domains of Leukemia-associated RhoGEF in complex with RhoA
1xcg	Crystal Structure of Human RhoA in complex with DH/PH fragment of PDZRHOGEF
1xd4	Crystal structure of the DH-PH-cat module of Son of Sevenless (SOS)
1xdv	Experimentally Phased Structure of Human the Son of Sevenless protein at 4.1 Ang.
1xx0	Structure of the C-terminal PH domain of human pleckstrin
1ym7	G Protein-Coupled Receptor Kinase 2 (GRK2)
1zc3	Crystal structure of the Ral-binding domain of Exo84 in complex with the active RalA
1zc4	Crystal structure of the Ral-binding domain of Exo84 in complex with the active RalA
1zm0	Crystal Structure of the Carboxyl Terminal PH Domain of Pleckstrin To 2.1 Angstroms
2adz	solution structure of the joined PH domain of alpha1-syntrophin
2bcj	Crystal Structure of G Protein-Coupled Receptor Kinase 2 in Complex with Galpha-q and Gbetagamma Subunits
2coa	Solution structure of the PH domain of protein kinase C, D2 type from human
2coc	Solution structure of the C-terminal PH domain of FYVE, RhoGEF and PH domain containing protein 3 (FGD3) from human
2cod	Solution structure of the N-terminal PH domain of ARAP2 protein from human
2cof	Solution structure of the C-terminal PH domain of hypothetical protein KIAA1914 from human
2d9v	Solution structure of the PH domain of Pleckstrin homology domain-containing protein family B member 1 from mouse
2d9w	Solution structure of the PH domain of Docking protein 2 from human
2d9x	Solution structure of the PH domain of Oxysterol binding protein-related protein 11 from human
2d9y	Solution structure of the PH domain of PEPP-3 from human
2d9z	Solution structure of the PH domain of Protein kinase C, nu type from human
2da0	Solution structure of the PH domain of PIP2-dependent ARF1 GTPase-activating protein from human
2dfk	Crystal structure of the CDC42-Collybistin II complex
2dhi	Solution structure of the PH domain of Evectin-2 from mouse
2dhj	Solution structure of the PH domain of Rho GTPase activating protein 21 from human
2dhk	Solution structure of the PH domain of TBC1 domain family member 2 protein from human
2dkp	Solution structure of the PH domain of pleckstrin homology domain-containing protein family A member 5 from human
2dn6	Solution structure of the PH domain of KIAA0640 protein from human
2dtc	Crystal structure of MS0666
2dx1	Crystal structure of RhoGEF protein Asef
2dyn	DYNAMIN (PLECKSTRIN HOMOLOGY DOMAIN) (DYNPH)
2elb	Crystal Structure of the BAR-PH domain of human APPL1
2fjl	Solution Structure of the Split PH domain in Phospholipase C-gamma1
2i5c	Crystal structure of the C-terminal PH domain of pleckstrin in complex with D-myo-Ins(1,2,3,4,5)P5
2i5f	Crystal structure of the C-terminal PH domain of pleckstrin in complex with D-myo-Ins(1,2,3,5,6)P5
2j59	Crystal structure of the ARF1:ARHGAP10-ArfBD complex
2k2j	NMR solution structure of the split PH domain from Phospholipase C gamma 2
2kcj	solution structure of FAPP1 PH domain
2lg1	Solution structure of the human AKAP13 PH domain and stabilizing DH helix
2lko	Structural Basis of Phosphoinositide Binding to Kindlin-2 Pleckstrin Homology Domain in Regulating Integrin Activation
2lul	Solution NMR Structure of PH Domain of Tyrosine-protein kinase Tec from Homo sapiens, Northeast Structural Genomics Consortium (NESG) Target HR3504C
2mdx	2MDX
2nz8	N-terminal DHPH cassette of Trio in complex with nucleotide-free Rac1
2otx	Crystal Structure of A N-terminal Fragment of SKAP-HOM Containing both the Helical Dimerization Domain and the PH Domain
2p0d	ArhGAP9 PH domain in complex with Ins(1,4,5)P3
2p0f	ArhGAP9 PH domain in complex with Ins(1,3,5)P3
2p0h	ArhGAP9 PH domain in complex with Ins(1,3,4)P3
2pz1	Crystal Structure of Auto-inhibited Asef
2q13	Crystal structure of BAR-PH domain of APPL1
2r09	Crystal Structure of Autoinhibited Form of Grp1 Arf GTPase Exchange Factor
2r0d	Crystal Structure of Autoinhibited Form of Grp1 Arf GTPase Exchange Factor
2rgn	Crystal Structure of p63RhoGEF complex with Galpha-q and RhoA
2rlo	Split PH domain of PI3-kinase enhancer
2rov	The split PH domain of ROCK II
2rsg	Solution structure of the CERT PH domain
2uvm	Structure of PKBalpha PH domain in complex with a novel inositol headgroup surrogate, benzene 1,2,3,4-tetrakisphosphate
2uzr	A transforming mutation in the pleckstrin homology domain of AKT1 in cancer (AKT1-PH_E17K)
2uzs	A transforming mutation in the pleckstrin homology domain of AKT1 in cancer (AKT1-PH_E17K)
2vrw	Critical structural role for the PH and C1 domains of the Vav1 exchange factor
2w2w	PLCg2 Split Pleckstrin Homology (PH) Domain
2w2x	Complex of Rac2 and PLCg2 spPH Domain
2x18	The crystal structure of the PH domain of human AKT3 protein kinase
2y7b	Crystal structure of the PH domain of human Actin-binding protein anillin ANLN
2yry	Solution structure of the PH domain of Pleckstrin homology domain-containing family A member 6 from human
2ys1	Solution structure of the PH domain of Dynamin-2 from human
2ys3	Solution structure of the PH domain of Kindlin-3 from human
2z0o	Crystal structure of APPL1-BAR-PH domain
2z0p	Crystal structure of PH domain of Bruton's tyrosine kinase
2z0q	Crystal structure of DH-PH domain of RhoGEF3(Xpln)
3a8n	Crystal structure of the Tiam1 PHCCEx domain
3a8p	Crystal structure of the Tiam2 PHCCEx domain
3a8q	Low-resolution crystal structure of the Tiam2 PHCCEx domain
3a98	Crystal structure of the complex of the interacting regions of DOCK2 and ELMO1
3aj4	Crystal structure of the PH domain of Evectin-2 from human complexed with O-phospho-L-serine
3bji	Structural Basis of Promiscuous Guanine Nucleotide Exchange by the T-Cell Essential Vav1
3cik	Human GRK2 in Complex with Gbetagamma subunits
3cxb	Crystal Structure of sifa and skip
3feh	Crystal structure of full length centaurin alpha-1
3fm8	Crystal structure of full length centaurin alpha-1 bound with the FHA domain of KIF13B (CAPRI target)
3hk0	Crystal Structure of the RA and PH Domains of Grb10
3hw2	Crystal structure of the SifA-SKIP(PH) complex
3jzy	Crystal structure of human Intersectin 2 C2 domain
3krw	Human GRK2 in complex with Gbetgamma subunits and balanol (soak)
3krx	Human GRK2 in complex with Gbetgamma subunits and balanol (co-crystal)
3ksy	Crystal structure of the Histone domain, DH-PH unit, and catalytic unit of the Ras activator Son of Sevenless (SOS)
3ky9	Autoinhibited Vav1
3kz1	Crystal Structure of the Complex of PDZ-RhoGEF DH/PH domains with GTP-gamma-S Activated RhoA
3lju	Crystal structure of full length centaurin alpha-1 bound with the head group of PIP3
3mdb	Crystal structure of the ternary complex of full length centaurin alpha-1, KIF13B FHA domain, and IP4
3ml4	Crystal structure of a complex between Dok7 PH-PTB and the MuSK juxtamembrane region
3mpx	Crystal structure of the DH and PH-1 domains of human FGD5
3nsu	A Systematic Screen for Protein-Lipid Interactions in Saccharomyces cerevisiae
3o96	Crystal Structure of Human AKT1 with an Allosteric Inhibitor
3odo	Crystal Structure of the DH/PH Domains of p115-RhoGEF
3odw	Crystal Structure of the Linker-DH/PH domains of p115-RhoGEF
3odx	Crystal Structure of an N-terminally Truncated Linker-DH/PH Domains of p115-RhoGEF
3p6a	Crystal Structure of the DH/PH domains of p115-RhoGEF (R399E mutant)
3pp2	Crystal structure of the pleckstrin homology domain of ArhGAP27
3psc	Bovine GRK2 in complex with Gbetagamma subunits
3pvu	Bovine GRK2 in complex with Gbetagamma subunits and a selective kinase inhibitor (CMPD101)
3pvw	Bovine GRK2 in complex with Gbetagamma subunits and a selective kinase inhibitor (CMPD103A)
3qbv	Structure of designed orthogonal interaction between CDC42 and nucleotide exchange domains of intersectin
3qr0	Crystal Structure of S. officinalis PLC21
3qr1	Crystal Structure of L. pealei PLC21
3qwm	Crystal Structure of GEP100, the plextrin homology domain of IQ motif and SEC7 domain-containing protein 1 isoform a
3rcp	Crystal structure of the FAPP1 pleckstrin homology domain
3snh	Crystal structure of nucleotide-free human dynamin1
3t06	Crystal Structure of the DH/PH fragment of PDZRHOGEF with N-terminal regulatory elements in complex with Human RhoA
3tca	Crystal structure of the Ras-associating and pleckstrin-homology domains of RIAM
3tfm	Myosin X PH1N-PH2-PH1C tandem
3uzs	Structure of the C13.28 RNA Aptamer Bound to the G Protein-Coupled Receptor Kinase 2-Heterotrimeric G Protein Beta 1 and Gamma 2 Subunit Complex
3uzt	Structure of the C13.18 RNA Aptamer in Complex with G Protein-Coupled Receptor Kinase 2
3v5w	Human G Protein-Coupled Receptor Kinase 2 in Complex with Soluble Gbetagamma Subunits and Paroxetine
3via	Crystal structure of the PH domain of Evectin-2 from human
3zvr	Crystal structure of Dynamin
3zys	Human dynamin 1 deltaPRD polymer stabilized with GMPPCP
4a5k	Structural analyses of Slm1-PH domain demonstrate ligand binding in the non-canonical site
4a6f	Crystal structure of Slm1-PH domain in complex with Phosphoserine
4a6h	Crystal structure of Slm1-PH domain in complex with Inositol-4- phosphate
4a6k	Crystal structure of Slm1-PH domain in complex with D-myo-Inositol-4- phosphate
4bbk	Structural and functional characterisation of the kindlin-1 pleckstrin homology domain
4c0a	Arf1(Delta1-17)in complex with BRAG2 Sec7-PH domain
4ckg	4CKG
4ckh	4CKH
4d0n	AKAP13 (AKAP-Lbc) RhoGEF domain in complex with RhoA
4ejn	Crystal structure of autoinhibited form of AKT1 in complex with N-(4-(5-(3-acetamidophenyl)-2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)-3-fluorobenzamide
4f7h	The crystal structure of kindlin-2 pleckstrin homology domain in free form
4gmv	Crystal Structure of the coiled-coil, RA and PH domains of Lamellipodin
4gn1	Crystal Structure of the RA and PH domains of Lamellipodin
4gzu	Crystal strucure of the DH-PH-PH domain of FARP2
4h6y	Crystal strucure of the DH-PH-PH domain of FARP1
4h8s	Crystal structure of human APPL2BARPH domain
4hhv	Crystal structure of ceramide transfer protein pleckstrin homology domain
4iap	Crystal structure of PH domain of Osh3 from Saccharomyces cerevisiae
4k2o	The Structure of a Triple Mutant of the Tiam1 PH-CC-Ex Domain
4k2p	The Structure of a Quintuple Mutant of the Tiam1 PH-CC-Ex Domain
4k81	Crystal structure of the Grb14 RA and PH domains in complex with GTP-loaded H-Ras
4kax	Crystal structure of the Grp1 PH domain in complex with Arf6-GTP
4kvg	Crystal structure of RIAM RA-PH domains in complex with GTP bound Rap1
4mk0	Crystal structure of G protein-coupled receptor kinase 2 in complex with a a rationally designed paroxetine derivative
4mt6	4MT6
4mt7	4MT7
4nsw	4NSW
4pnk	4PNK
4uud	4UUD
4uuk	4UUK
4xh3	4XH3
4xh9	4XH9
4xoh	4XOH
4y93	4Y93
4y94	4Y94
4yon	4YON
5a3f	5A3F
5c5b	5C5B
5c6r	5C6R
5c79	5C79
5d27	5D27
5d3v	5D3V
5d3w	5D3W
5d3x	5D3X
5d3y	5D3Y
5efx	5EFX
5fi0	5FI0
5fi1	5FI1
5he0	5HE0
5he1	5HE1
5he2	5HE2
5he3	5HE3
5kcv	5KCV

Links (links to other resources describing this domain)

• PROSITE: PH_DOMAIN
• PFAM: PH
• INTERPRO: IPR001849