Summary: Transcription factor TFIIH complex subunit Tfb5
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This is the Wikipedia entry entitled "Tbf5 protein domain". More...
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Tbf5 protein domain Edit Wikipedia article
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Crystal structure of the human TFIIH.
In molecular biology, this protein domain represents Tbf5 which stands for TTDA subunit of TFIIH basal transcription factor complex (also known as subunit 5 of RNA polymerase II transcription factor B), and Rex1 a type of nucleotide excision repair (NER) proteins. Nucleotide excision repair is a major pathway for repairing UV light-induced DNA damage in most organisms. The function of this protein is to aid transcription.
Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair. The TFIIH complex consists of ten subunits:
- CDK7 and
TTDA is also required for the stability of the TFIIH complex and for the presence of normal levels of TFIIH in the cell. TFIIH is one of five general transcription factors (GTFs) that assemble with RNA polymerase IIat a promoter site prior to the initiation of transcription. It is one of ten subunits that complete part of the 10 subunit protein complex (holoTFIIH) and part of a six-subunit complex of Rad3, Tfb1, Tfb2, Tfb4, Tfb5, and Ssl1 (referred to as core) 
In humans, the function of Tbf5 is clear, as loss of it leads to trichothiosystropy. Defects in GTF2H5 cause the disease trichothiodystrophy (TTD), therefore GTF2H5 (general transcription factor 2H subunit 5) is also known as the TTD group A (TTDA) subunit (and as Tfb5). The TTDA subunit is responsible for the DNA repair function of the complex. TTDA is present both bound to TFIIH, and as a free fraction that shuffles between the cytoplasm and nucleus; induction of NER-type DNA lesions shifts the balance towards TTDA's more stable association with TFIIH.
- Gibbons BJ, Brignole EJ, Azubel M, Murakami K, Voss NR, Bushnell DA, et al. (2012). "Subunit architecture of general transcription factor TFIIH.". Proc Natl Acad Sci U S A. 109 (6): 1949–54. doi:10.1073/pnas.1105266109. PMC . PMID 22308316.
- Giglia-Mari G, Coin F, Ranish JA, Hoogstraten D, Theil A, Wijgers N, Jaspers NG, Raams A, Argentini M, van der Spek PJ, Botta E, Stefanini M, Egly JM, Aebersold R, Hoeijmakers JH, Vermeulen W (July 2004). "A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A". Nat. Genet. 36 (7): 714–9. doi:10.1038/ng1387. PMID 15220921.
- Giglia-Mari G, Miquel C, Theil AF, Mari PO, Hoogstraten D, Ng JM, Dinant C, Hoeijmakers JH, Vermeulen W (June 2006). "Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells". PLoS Biol. 4 (6): e156. doi:10.1371/journal.pbio.0040156. PMC . PMID 16669699.
- Cenkci B, Petersen JL, Small GD (June 2003). "REX1, a novel gene required for DNA repair". J. Biol. Chem. 278 (25): 22574–7. doi:10.1074/jbc.M303249200. PMID 12697762.
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.
Transcription factor TFIIH complex subunit Tfb5 Provide feedback
This family is a component of the general transcription and DNA repair factor IIH. TFB5 has been shown to be required for efficient recruitment of TFIIH to a promoter .
Blandin G, Durrens P, Tekaia F, Aigle M, Bolotin-Fukuhara M, Bon E, Casaregola S, de Montigny J, Gaillardin C, Lepingle A, Llorente B, Malpertuy A, Neuveglise C, Ozier-Kalogeropoulos O, Perrin A, Potier S, Souciet J, Talla E, Toffano-Nioche C, Wesolowski-, FEBS Lett 2000;487:31-36.: Genomic exploration of the hemiascomycetous yeasts: 4. The genome of Saccharomyces cerevisiae revisited. PUBMED:11152879 EPMC:11152879
Ranish JA, Hahn S, Lu Y, Yi EC, Li XJ, Eng J, Aebersold R; , Nat Genet. 2004;36:707-713.: Identification of TFB5, a new component of general transcription and DNA repair factor IIH. PUBMED:15220919 EPMC:15220919
This tab holds annotation information from the InterPro database.
InterPro entry IPR009400
This entry represents TTDA/Tfb5 subunit of TFIIH basal transcription factor complex. These proteins have a structural motif consisting of a 2-layer sandwich structure with an alpha/beta plait topology. Nucleotide excision repair is a major pathway for repairing UV light-induced DNA damage in most organisms.
Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair. The TFIIH multiprotein complex consists of a 7-subunit core (XPB, p62, p52, p44, p34, and TTDA) that is associated with a 3-subunit CDK-activating kinase module (MAT1, cyclin H and Cdk7) [PUBMED:21592869].
In humans, defects in TTDA cause the trichothiodystrophy photosensitive (TTDP), an autosomal recessive disease characterised by sulfur-deficient brittle hair and nails, ichthyosis, mental retardation, impaired sexual development, abnormal facies and cutaneous photosensitivity correlated with a nucleotide excision repair (NER) defect [PUBMED:15220921].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||core TFIIH complex (GO:0000439)|
|Biological process||regulation of transcription, DNA-templated (GO:0006355)|
|nucleotide-excision repair (GO:0006289)|
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:
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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
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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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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
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|Previous IDs:||REX1; Tbf5;|
|Author:||Studholme DJ , Wood V|
|Number in seed:||89|
|Number in full:||914|
|Average length of the domain:||65.20 aa|
|Average identity of full alignment:||34 %|
|Average coverage of the sequence by the domain:||68.19 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -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.
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There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
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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
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The tree shows the occurrence of this domain across different species. More...
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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.
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There is 1 interaction 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 Tfb5 domain has been found. There are 16 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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