Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
0  structures 148  species 0  interactions 249  sequences 24  architectures

Family: PH_10 (PF15411)

Summary: Pleckstrin homology domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Pleckstrin homology domain". More...

Pleckstrin homology domain Edit Wikipedia article

1bwn opm.gif
PH domain of tyrosine-protein kinase BTK
Identifiers
Symbol PH
Pfam PF00169
InterPro IPR001849
SMART PH
PROSITE PDOC50003
SCOP 1dyn
SUPERFAMILY 1dyn
OPM superfamily 51
OPM protein 1pls
CDD cd00821

Pleckstrin homology domain (PH domain) is a protein domain of approximately 120 amino acids 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]

This domain can bind Phosphatidylinositol lipids within biological membranes (such as Phosphatidylinositol (3,4,5)-trisphosphate and phosphatidylinositol (4,5)-bisphosphate),[8] and proteins such as the βγ-subunits of heterotrimeric G proteins,[9] and protein kinase C.[10] 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.

Lipid binding specificity[edit]

Individual PH domains possess specificities for phosphoinositides phosphorylated at different sites within the inositol ring, e.g., some bind phosphatidylinositol (4,5)-bisphosphate but not phosphatidylinositol (3,4,5)-trisphosphate or phosphatidylinositol (3,4)-bisphosphate, while others may possess the requisite affinity. This is important because it makes the recruitment of different PH domain containing proteins sensitive to the activities of enzymes that either phosphorylate or dephosphorylate these sites on the inositol ring, such as phosphoinositide 3-kinase or PTEN, respectively. Thus, such enzymes exert a part of their effect on cell function by modulating the localization of downstream signaling proteins that possess PH domains that are capable of binding their phospholipid products.

Structure[edit]

The 3D structure of several PH domains has been determined.[11] 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 while providing the source of the domain's specificity. The only conserved residue among PH domains is a single tryptophan located within the alpha helix that serves to nucleate the core of the domain.

Proteins containing PH domain[edit]

PH domains can be found in many different proteins, such as OSBP or ARF. Recruitment to the Golgi 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 .[12] 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 is one of the rare proteins to contain 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 S. 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.
  • Ceramide kinase, a lipid kinase that phosphorylates ceramides to ceramide-1-phosphate.[13]

Subfamilies[edit]

Examples[edit]

Human genes encoding proteins containing this domain include:

See also[edit]

References[edit]

  1. ^ Mayer, B. J.; Ren, R.; Clark, K. L.; Baltimore, D. (1993). "A putative modular domain present in diverse signaling proteins". Cell 73 (4): 629–630. doi:10.1016/0092-8674(93)90244-K. PMID 8500161.  edit
  2. ^ Haslam, R. J.; Koide, H. B.; Hemmings, B. A. (1993). "Pleckstrin domain homology". Nature 363 (6427): 309. doi:10.1038/363309b0.  edit
  3. ^ Musacchio, A.; Gibson, T.; Rice, P.; Thompson, J.; Saraste, M. (1993). "The PH domain: A common piece in the structural pathcwork of signalling proteins". Trends in Biochemical Sciences 18 (9): 343–348. doi:10.1016/0968-0004(93)90071-T. PMID 8236453.  edit
  4. ^ Gibson, T. J.; Hyvönen, M.; Musacchio, A.; Saraste, M.; Birney, E. (1994). "PH domain: The first anniversary". Trends in Biochemical Sciences 19 (9): 349–353. doi:10.1016/0968-0004(94)90108-2. PMID 7985225.  edit
  5. ^ Pawson, T. (1995). "Protein modules and signalling networks". Nature 373 (6515): 573–580. doi:10.1038/373573a0. PMID 7531822.  edit
  6. ^ Ingley, E.; Hemmings, B. A. (1994). "Pleckstrin homology (PH) domains in signal transducton". Journal of Cellular Biochemistry 56 (4): 436–443. doi:10.1002/jcb.240560403. PMID 7890802.  edit
  7. ^ Saraste, M.; Hyvönen, M. (1995). "Pleckstrin homology domains: A fact file". Current Opinion in Structural Biology 5 (3): 403–408. doi:10.1016/0959-440X(95)80104-9. PMID 7583640.  edit
  8. ^ Wang, D. S.; Shaw, G. (1995). "The Association of the C-Terminal Region of β1ΣII Spectrin to Brain Membranes is Mediated by a pH Domain, Does Not Require Membrane Proteins, and Coincides with a Inositol-1,4,5 Trisphosphate Binding Site". Biochemical and Biophysical Research Communications 217 (2): 608–615. doi:10.1006/bbrc.1995.2818. PMID 7503742.  edit
  9. ^ Wang, D. S.; Shaw, R.; Winkelmann, J. C.; Shaw, G. (1994). "Binding of PH Domains of β-Adrenergic-Receptor Kinase and β-Spectrin to WD40/β-Transducin Repeat Containing Regions of the β-Subunit of Trimeric G-Proteins". Biochemical and Biophysical Research Communications 203 (1): 29–35. doi:10.1006/bbrc.1994.2144. PMID 8074669.  edit
  10. ^ Yao, L.; Kawakami, Y.; Kawakami, T. (1994). "The pleckstrin homology domain of Bruton tyrosine kinase interacts with protein kinase C". Proceedings of the National Academy of Sciences 91 (19): 9175. doi:10.1073/pnas.91.19.9175.  edit
  11. ^ Riddihough, G. (1994). "More meanders and sandwiches". Nature Structural Biology 1 (11): 755–757. doi:10.1038/nsb1194-755. PMID 7634082.  edit
  12. ^ Yu, J. W.; Mendrola, J. M.; Audhya, A.; Singh, S.; Keleti, D.; Dewald, D. B.; Murray, D.; Emr, S. D.; Lemmon, M. A. (2004). "Genome-Wide Analysis of Membrane Targeting by S. Cerevisiae Pleckstrin Homology Domains". Molecular Cell 13 (5): 677–688. doi:10.1016/S1097-2765(04)00083-8. PMID 15023338.  edit
  13. ^ Sugiura, M.; Kono, K.; Liu, H.; Shimizugawa, T.; Minekura, H.; Spiegel, S.; Kohama, T. (2002). "Ceramide Kinase, a Novel Lipid Kinase. MOLECULAR CLONING AND FUNCTIONAL CHARACTERIZATION". Journal of Biological Chemistry 277 (26): 23294–23300. doi:10.1074/jbc.M201535200. PMID 11956206.  edit

External links[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Pleckstrin homology domain Provide feedback

This Pleckstrin homology domain is found in some fungal species.

Literature references

  1. Gibson TJ, Hyvonen M, Musacchio A, Saraste M, Birney E; , Trends Biochem Sci 1994;19:349-353.: PH domain: the first anniversary. PUBMED:7985225 EPMC:7985225


Internal database links

External database links

This tab holds annotation information from the InterPro database.

No InterPro data for this Pfam family.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(39)
Full
(249)
Representative proteomes NCBI
(253)
Meta
(0)
RP15
(52)
RP35
(101)
RP55
(157)
RP75
(185)
Jalview View  View  View  View  View  View  View   
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(39)
Full
(249)
Representative proteomes NCBI
(253)
Meta
(0)
RP15
(52)
RP35
(101)
RP55
(157)
RP75
(185)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(39)
Full
(249)
Representative proteomes NCBI
(253)
Meta
(0)
RP15
(52)
RP35
(101)
RP55
(157)
RP75
(185)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

This family is new in this Pfam release.

Seed source: Jackhmmer:P40995
Previous IDs: none
Type: Domain
Author: Wood V, Coggill P
Number in seed: 39
Number in full: 249
Average length of the domain: 117.60 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 12.77 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.5 27.5
Trusted cut-off 27.7 27.5
Noise cut-off 27.1 26.8
Model length: 116
Family (HMM) version: 1
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.