Summary

T-box

The T-box encodes a 180 amino acid domain that binds to DNA. Genes encoding T-box proteins are found in a wide range of animals, but not in other kingdoms such as plants. Family members are all thought to bind to the DNA consensus sequence TCACACCT. they are found exclusively in the nucleus, and perform DNA-binding and transcriptional activation/repression roles. They are generally required for development of the specific tissues they are expressed in, and mutations in T-box genes are implicated in human conditions such as DiGeorge syndrome and X-linked cleft palate, which feature malformations [2].

Literature references

Muller CW, Herrmann BG; , Nature 1997;389:884-888.: Crystallographic structure of the T domain-DNA complex of the Brachyury transcription factor. PUBMED:9349824
Wilson V, Conlon FL; , Genome Biol 2002;3:REVIEWS3008.: The T-box family. PUBMED:12093383

InterPro entry IPR001699

Transcription factors of the T-box family are required both for early cell-fate decisions, such as those necessary for formation of the basic vertebrate body plan, and for differentiation and organogenesis PUBMED:12093383. The T-box is defined as the minimal region within the T-box protein that is both necessary and sufficient for sequence-specific DNA binding, all members of the family so far examined bind to the DNA consensus sequence TCACACCT. The T-box is a relatively large DNA-binding domain, generally comprising about a third of the entire protein (17-26 kDa).

These genes were uncovered on the basis of similarity to the DNA binding domain PUBMED:9504043 of Mus musculus (Mouse) Brachyury (T) gene product, which similarity is the defining feature of the family. The Brachyury gene is named for its phenotype, which was identified 70 years ago as a mutant mouse strain with a short blunted tail. The gene, and its paralogues, have become a well-studied model for the family, and hence much of what is known about the T-box family is derived from the murine Brachyury gene.

Consistent with its nuclear location, Brachyury protein has a sequence-specific DNA-binding activity and can act as a transcriptional regulator PUBMED:9503012. Homozygous mutants for the gene undergo extensive developmental anomalies, thus rendering the mutation lethal PUBMED:9395282. The postulated role of Brachyury is as a transcription factor, regulating the specification and differentiation of posterior mesoderm during gastrulation in a dose-dependent manner PUBMED:9504043.

T-box proteins tend to be expressed in specific organs or cell types, especially during development, and they are generally required for the development of those tissues, for example, Brachyury is expressed in posterior mesoderm and in the developing notochord, and it is required for the formation of these cells in mice PUBMED:9196325.

Clan

This family is a member of clan P53-like (CL0073), which contains the following 6 members:

NDT80_PhoG P53 RHD Runt STAT_bind T-box

Gene Ontology

Cellular component	nucleus (GO:0005634)
Molecular function	transcription factor activity (GO:0003700)
Biological process	regulation of transcription, DNA-dependent (GO:0006355)

External database links

PANDIT:	PF00907
PROSITE:	PDOC00972
SCOP:	1xbr
SYSTERS:	T-box

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

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (22) Full (856) NCBI (1142) Metagenomics
Viewer:

Formatting options

Alignment:	Seed (22) Full (856)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

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

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (22) Full (856) NCBI (1142) Metagenomics
Full length sequences	Full-sequences (856)

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 HMMER2.

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. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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:

Pfam-B_363 (release 3.0)

Previous IDs:

none

Type:

Domain

Author:

Bateman A

Number in seed:

22

Number in full:

856

Average length of the domain:

146.40 aa

Average identity of full alignment:

48 %

Average coverage of the sequence by the domain:

37.55 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.5	20.5
Trusted cut-off	21.7	20.6
Noise cut-off	20.1	19.1

Model length:

183

Family (HMM) version:

15

Download:

download the raw HMM for this family

Species distribution

Tree controls

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

Species trees

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.

Interactive tree

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
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Interactions

There is 1 interaction for this family. More...

T-box

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 T-box domain has been found.

Loading structure mapping...

Family: T-box (PF00907)

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Summary

T-box

Literature references

InterPro entry IPR001699

Clan

Gene Ontology

External database links

Domain organisation

Alignments

Viewing

Downloading

View options

Formatting options

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Interactions

Structures