Summary

Tissue factor

This is a fibronectin type III domain.

Literature references

Muller YA, Ultsch MH, de Vos AM; , J Mol Biol 1996;256:144-159.: The crystal structure of the extracellular domain of human tissue factor refined to 1.7 A resolution. PUBMED:8609606

InterPro entry IPR001187

Tissue factor (TF, also known as thromboplastin) is an integral membrane glycoprotein that initiates blood coagulation by forming a complex with circulating factor VII (FVII) or VIIa (FVIIa), which it comes in contact with following damage to blood vessel walls. Calcium forms the bridge between TF and FVII, the resultant TF/FVII undergoing auto-cleavage to produce activated TF/FVIIa. This activation sets off an extracellular cascade involving sequential serine protease activations, where TF/FVIIa converts FIX to FIXa, followed by a series of reactions to finally produce fibrin, leading to fibrin deposition and the activation of platelets to form clots PUBMED:15569823, PUBMED:16261634.

Tissue Factor plays many diverse roles, and in addition to promoting blood coagulation, it is involved in inflammation, embryonic development, angiogenesis, tumour metastasis, cell adhesion/migration, and innate immunity PUBMED:16479459. For example, TF plays an important role in inflammation, since the extracellular blood coagulation signalling pathway can trigger an intracellular inflammation-signalling pathway PUBMED:16036212, PUBMED:14872439. TF activation leads to the production of activated factors FVIIa, FXa and FIIa, which in turn can activate PAR (protease-activated receptors) receptors, resulting in the expression of a variety of inflammatory molecules.

The extracellular domain of tissue factor, which accounts for over 80% of the protein, contains two domains with the same structural fold as fibronectin type III, consisting of an immunoglobulin-like beta-sandwich with a Greek key topology.

More information about these protein can be found at Protein of the Month: Tissue Factor PUBMED:.

Clan

This family is a member of clan E-set (CL0159), which contains the following 43 members:

A2M_N Alpha_adaptinC2 Big_1 Big_2 Big_3 Big_4 BiPBP_C Bre5 Cadherin Cadherin_2 Cadherin_pro CARDB ChitinaseA_N DUF1034 DUF11 DUF1927 DUF1973 DUF916 EpoR_lig-bind Filamin fn3 He_PIG HYR IFNGR1 IL6Ra-bind Integrin_alpha2 Interfer-bind Invasin_D3 MG1 Neurexophilin NPCBM_assoc phage_tail_N Pili_assembly_N PKD PPC REJ Rib SoxZ TIG Tissue_fac Transglut_C TRAP_beta Y_Y_Y

Gene Ontology

Cellular component	integral to membrane (GO:0016021)
Biological process	blood coagulation (GO:0007596)

Internal database links

SCOOP:

C2-set Sp38 Y_Y_Y C2-set_2 Interfer-bind

External database links

HOMSTRAD:	fn3
PANDIT:	PF01108
PROSITE:	PDOC00541
SCOP:	2hft
SYSTERS:	Tissue_fac

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 (61) Full (273) NCBI (1873) Metagenomics (18)
Viewer:

Formatting options

Alignment:	Seed (61) Full (273)
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 (61) Full (273) NCBI (1873) Metagenomics (18)
Full length sequences	Full-sequences (273)

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:

Prosite

Previous IDs:

none

Type:

Family

Author:

Finn RD, Bateman A

Number in seed:

61

Number in full:

273

Average length of the domain:

101.90 aa

Average identity of full alignment:

22 %

Average coverage of the sequence by the domain:

26.07 %

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	20.5	20.5
Noise cut-off	20.4	20.4

Model length:

107

Family (HMM) version:

10

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 are 2 interactions for this family. More...

Tissue_fac C1-set

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 Tissue_fac domain has been found.

Loading structure mapping...

Family: Tissue_fac (PF01108)

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