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10  structures 1271  species 0  interactions 5509  sequences 117  architectures

Family: PH_12 (PF16457)

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

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.

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.

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Literature references

  1. 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

  2. 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

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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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 (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)
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: ✓ available, x not generated, not available.

Format an alignment

  Seed
(60)
Full
(5509)
Representative proteomes UniProt
(8965)
RP15
(639)
RP35
(1790)
RP55
(4056)
RP75
(5625)
Alignment:
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Order:
Sequence:
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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
(60)
Full
(5509)
Representative proteomes UniProt
(8965)
RP15
(639)
RP35
(1790)
RP55
(4056)
RP75
(5625)
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.

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

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 View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 27.0 27.0
Noise cut-off 26.9 26.9
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.

Protein Predicted structure External Information
A0A044VBV8 View 3D Structure Click here
A0A077Z5L2 View 3D Structure Click here
A0A0D2GQV9 View 3D Structure Click here
A0A0G2KRJ3 View 3D Structure Click here
A0A0K0E3E1 View 3D Structure Click here
A0A0K0EF02 View 3D Structure Click here
A0A0N4U7S9 View 3D Structure Click here
A0A0R0GIK8 View 3D Structure Click here
A0A0R0IEG5 View 3D Structure Click here
A0A0R0IUD7 View 3D Structure Click here
A0A0R0KPM3 View 3D Structure Click here
A0A0R4IHP8 View 3D Structure Click here
A0A158Q6H7 View 3D Structure Click here
A0A175W9H4 View 3D Structure Click here
A0A1C1CKA5 View 3D Structure Click here
A0A1D6E1T8 View 3D Structure Click here
A0A1D6E4Z3 View 3D Structure Click here
A0A1D6G2V2 View 3D Structure Click here
A0A1D6HG44 View 3D Structure Click here
A0A1D6Q734 View 3D Structure Click here
A0A1I9LTP1 View 3D Structure Click here
A0A1P8BCA2 View 3D Structure Click here
A0A2K6VMX8 View 3D Structure Click here
A0A2R8PZX9 View 3D Structure Click here
A0A2R8RJ32 View 3D Structure Click here
A0A2R8RVV2 View 3D Structure Click here
A0A3P7DPL6 View 3D Structure Click here
A0A3P7FQF7 View 3D Structure Click here
A2AP18 View 3D Structure Click here
A4FUD6 View 3D Structure Click here
A6QR40 View 3D Structure Click here
A8XEZ1 View 3D Structure Click here
C0NKN6 View 3D Structure Click here
C1GTB3 View 3D Structure Click here
D4AAX6 View 3D Structure Click here
E7F8G4 View 3D Structure Click here
F1M324 View 3D Structure Click here
F1QAP6 View 3D Structure Click here
F1QSV8 View 3D Structure Click here
F4JVE8 View 3D Structure Click here