Summary: Pleckstrin homology domain
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This is the Wikipedia entry entitled "Pleckstrin homology domain". More...
Pleckstrin homology domain Edit Wikipedia article
Pleckstrin homology domain (PH domain) is a protein region of approximately 120 amino acids that can bind phosphoinositides (such as inositol 1, 4, 5-trisphosphate and phosphatidylinositol 4, 5-bisphosphate), the βγ-subunits of heterotrimeric G proteins and protein kinase C. Through these interactions, the PH domain plays a role in thr membrane recruitment of proteins containing the PH domain, thus targeting them to appropriate cellular compartment or enabling them to interact with other components of the signal transduction pathways.
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Literature references
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Hanawa-Suetsugu K, Kukimoto-Niino M, Mishima-Tsumagari C, Akasaka R, Ohsawa N, Sekine S, Ito T, Tochio N, Koshiba S, Kigawa T, Terada T, Shirouzu M, Nishikimi A, Uruno T, Katakai T, Kinashi T, Kohda D, Fukui Y, Yokoyama S;, Proc Natl Acad Sci U S A. 2012;109:3305-3310.: Structural basis for mutual relief of the Rac guanine nucleotide exchange factor DOCK2 and its partner ELMO1 from their autoinhibited forms. PUBMED:22331897 EPMC:22331897
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Komander D, Patel M, Laurin M, Fradet N, Pelletier A, Barford D, Cote JF;, Mol Biol Cell. 2008;19:4837-4851.: An alpha-helical extension of the ELMO1 pleckstrin homology domain mediates direct interaction to DOCK180 and is critical in Rac signaling. PUBMED:18768751 EPMC:18768751
Internal database links
SCOOP: | PH PH_14 |
Similarity to PfamA using HHSearch: | Mcp5_PH ZFYVE21_C PH_14 |
This tab holds annotation information from the InterPro database.
InterPro entry 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 INTERPRO ), Caenorhabditis elegans kinesin-like protein unc-104 (see INTERPRO ), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1.
- Mammalian phosphatidylinositol-specific phospholipase C (PI-PLC) (see INTERPRO ) 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.
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan PH (CL0266), which has the following description:
Members of this clan share a PH-like fold. Many families in this clan bind to short peptide motifs in proteins and are involved in signalling.
The clan contains the following 87 members:
ASK_PH BBL5 bPH_1 bPH_2 bPH_3 bPH_4 bPH_5 bPH_6 CARM1 Carm_PH Cybc1_Eros DCP1 DM10_dom DUF1681 DUF2244 DUF2550 DUF3093 DUF3203 DUF3389 DUF5629 DUF5673 DUF956 DUF986 EbsA FERM_C Glycoprot_B_PH1 Glycoprot_B_PH2 GRAM hSac2 ICAP-1_inte_bdg Inp1 INPP5B_PH IQ_SEC7_PH IRS ISP1_C ISP3_C Jak1_Phl Mcp5_PH Meiotic_rec114 Myosin_TH1 OCRL_clath_bd PH PH_10 PH_11 PH_12 PH_13 PH_14 PH_15 PH_16 PH_17 PH_18 PH_19 PH_2 PH_20 PH_3 PH_4 PH_5 PH_6 PH_8 PH_9 PH_BEACH PH_RBD PH_TFIIH PID PID_2 POB3_N Proteasom_Rpn13 PTB Ran_BP1 Rtt106 SCAB-PH Sec3-PIP2_bind Sharpin_PH SIN1_PH SNX17_FERM_C SPT16 SSrecog SYCP2_SLD UCH_N VID27_N VID27_PH Voldacs Vps36_ESCRT-II WH1 Ycf4 YcxB ZFYVE21_CAlignments
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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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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 (60) |
Full (5509) |
Representative proteomes | UniProt (8965) |
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RP15 (639) |
RP35 (1790) |
RP55 (4056) |
RP75 (5625) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
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Seed (60) |
Full (5509) |
Representative proteomes | UniProt (8965) |
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---|---|---|---|---|---|---|---|
RP15 (639) |
RP35 (1790) |
RP55 (4056) |
RP75 (5625) |
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Raw Stockholm | |||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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
Seed source: | PDB:2vsz |
Previous IDs: | none |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Eberhardt R |
Number in seed: | 60 |
Number in full: | 5509 |
Average length of the domain: | 122.5 aa |
Average identity of full alignment: | 32 % |
Average coverage of the sequence by the domain: | 14.03 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 134 | ||||||||||||
Family (HMM) version: | 8 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PH_12 domain has been found. There are 10 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.