Summary: Pou domain - N-terminal to homeobox domain
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POU domain Edit Wikipedia article
|Pou domain - N-terminal to homeobox domain|
The acronym POU is derived from the names of three transcription factors:
- the Pituitary-specific Pit-1
- the Octamer transcription factor proteins Oct-1 and Oct-2 (octamer sequence is ATGCAAAT)
- the neural Unc-86 transcription factor from Caenorhabditis elegans.
There is a surprisingly high degree of amino acid sequence conservation (37%-42%) of POU homeodomains to the transcriptional regulator comS from the gram positive prokaryote Bacillus subtilis. Interestingly, akin to the way that POU homeodomain regulators lead to tissue differentiation in metazoans, this transcription factor is critical for differentiation of a subpopulation of B. subtilis into a state of genetic competence.
POU proteins are eukaryotic transcription factors containing a bipartite DNA binding domain referred to as the POU domain. The acronym POU (pronounced 'pow') is derived from the names of three transcription factors, the pituitary-specific Pit-1, the octamer-binding proteins Oct-1 and Oct-2, and the neural Unc-86 from Caenorhabditis elegans. POU domain genes have been described in organisms as divergent as Caenorhabditis elegans, Drosophila, Xenopus, zebrafish and human but have not been yet identified in plants and fungi. The various members of the POU family have a wide variety of functions, all of which are related to the function of the neuroendocrine system and the development of an organism. Some other genes are also regulated, including those for immunoglobulin light and heavy chains (Oct-2), and trophic hormone genes, such as those for prolactin and growth hormone (Pit-1).
The POU domain is a bipartite domain composed of two subunits separated by a non-conserved region of 15-55 aa. The N-terminal subunit is known as the POU-specific (POUs) domain (IPR000327), while the C-terminal subunit is a homeobox domain (IPR007103). 3D structures of complexes including both POU subdomains bound to DNA are available. Both subdomains contain the structural motif 'helix-turn-helix', which directly associates with the two components of bipartite DNA binding sites, and both are required for high affinity sequence-specific DNA-binding. The domain may also be involved in protein-protein interactions. The subdomains are connected by a flexible linker. In proteins a POU-specific domain is always accompanied by a homeodomain. Despite of the lack of sequence homology, 3D structure of POUs is similar to 3D structure of bacteriophage lambda repressor and other members of HTH_3 family.
Human genes encoding proteins containing the POU domain include:
- POU2F1; POU2F2; POU2F3;
- POU3F1; POU3F2; POU3F3; POU3F4;
- POU4F1; POU4F2; POU4F3;
- POU5F1; POU5F1P1; POU5F1P3; POU5F1P4; POU5F2;
- Phillips K, Luisi B (2000). "The virtuoso of versatility: POU proteins that flex to fit". J. Mol. Biol. 302 (5): 1023â39. doi:10.1006/jmbi.2000.4107. PMID 11183772.
- D'Souza C, Nakano MM, Zuber P (September 1994). "Identification of comS, a gene of the srfA operon that regulates the establishment of genetic competence in Bacillus subtilis". Proc. Natl. Acad. Sci. U.S.A. 91 (20): 9397â401. doi:10.1073/pnas.91.20.9397. PMC 44819. PMID 7937777.
- Assa-Munt N, Mortishire-Smith RJ, Aurora R, Herr W, Wright PE (1993). "The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain". Cell 73 (1): 193â205. doi:10.1016/0092-8674(93)90171-L. PMID 8462099.
- Rosenfeld MG, Andersen B (2001). "POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease". Endocr. Rev. 22 (1): 2â35. doi:10.1210/er.22.1.2. PMID 11159814.
- Petryniak B, Thompson CB, Staudt LM, Postema CE, McCormack WT (1990). "Characterization of chicken octamer-binding proteins demonstrates that POU domain-containing homeobox transcription factors have been highly conserved during vertebrate evolution". Proc. Natl. Acad. Sci. U.S.A. 87 (3): 1099â1103. doi:10.1073/pnas.87.3.1099. PMC 53418. PMID 1967834.
- Hirsh J, Johnson WA (1990). "Binding of a Drosophila POU-domain protein to a sequence element regulating gene expression in specific dopaminergic neurons". Nature 343 (6257): 467â470. doi:10.1038/343467a0. PMID 1967821.
- Mathis JM, Simmons DM, He X, Swanson LW, Rosenfeld MG (1992). "Brain 4: a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression". EMBO J. 11 (7): 2551â2561. PMC 556730. PMID 1628619.
- Phillips K, Luisi B (2000). "The virtuoso of versatility: POU proteins that flex to fit". J. Mol. Biol. 302 (5): 1023â1039. doi:10.1006/jmbi.2000.4107. PMID 11183772.
- Pabo CO, Aurora R, Herr W, Klemm JD, Rould MA (1994). "Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules". Cell 77 (1): 21â32. doi:10.1016/0092-8674(94)90231-3. PMID 8156594.
- Rosenfeld MG, Aggarwal AK, Li P, Jacobson EM, Leon-del-Rio A (1997). "Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility". Genes Dev. 11 (2): 198â212. doi:10.1101/gad.11.2.198. PMID 9009203.
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Pou domain - N-terminal to homeobox domain Provide feedback
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Internal database links
|Similarity to PfamA using HHSearch:||HTH_3 HTH_19 HTH_31|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR000327
POU proteins are eukaryotic transcription factors containing a bipartite DNA binding domain referred to as the POU domain. The acronym POU (pronounced 'pow') is derived from the names of three mammalian transcription factors, the pituitary-specific Pit-1, the octamer-binding proteins Oct-1 and Oct-2, and the neural Unc-86 from Caenorhabditis elegans. POU domain genes have been identified in diverse organisms including nematodes, flies, amphibians, fish and mammals but have not been yet identified in plants and fungi. The various members of the POU family have a wide variety of functions, all of which are related to the function of the neuroendocrine system [PUBMED:8462099] and the development of an organism [PUBMED:11159814]. Some other genes are also regulated, including those for immunoglobulin light and heavy chains (Oct-2) [PUBMED:1967834, PUBMED:1967821], and trophic hormone genes, such as those for prolactin and growth hormone (Pit-1).
The POU domain is a bipartite domain composed of two subunits separated by a non-conserved region of 15-55 aa. The N-terminal subunit is known as the POU-specific (POUs) domain (INTERPRO), while the C-terminal subunit is a homeobox domain (INTERPRO). 3D structures of complexes including both POU subdomains bound to DNA are available. Both subdomains contain the structural motif 'helix-turn-helix', which directly associates with the two components of bipartite DNA binding sites, and both are required for high affinity sequence-specific DNA-binding. The domain may also be involved in protein-protein interactions [PUBMED:1628619]. The subdomains are connected by a flexible linker [PUBMED:11183772, PUBMED:8156594, PUBMED:9009203]. In proteins a POU-specific domain is always accompanied by a homeodomain. Despite of the lack of sequence homology, 3D structure of POUs is similar to 3D structure of bacteriophage lambda repressor and other members of HTH_3 family [PUBMED:11183772, PUBMED:8156594].
This entry represents the POU-specific subunit of the POU domain.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||sequence-specific DNA binding transcription factor activity (GO:0003700)|
|Biological process||regulation of transcription, DNA-dependent (GO:0006355)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
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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...
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We make a range of alignments for each Pfam-A family:
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- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
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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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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.
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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.
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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.
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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.
|Number in seed:||20|
|Number in full:||1357|
|Average length of the domain:||69.20 aa|
|Average identity of full alignment:||59 %|
|Average coverage of the sequence by the domain:||18.40 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||12|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
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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.
There are 3 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 Pou domain has been found. There are 22 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 seqence.
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