Tissue Factor

Family Ties

Tissue Factor belongs to the fibronectin type-III superfamily, a large group of proteins that share the same structural fold, namely an immunoglobulin-like beta-sandwich with Greek key topology. The extracellular region of Tissue Factor, which accounts for over 80% of the protein, contains a two such fibronectin type-III domains. Other proteins containing fibronectin type-III domains include fibronectin, tenascin, neuorglian, neural cell adhesion molecule (NCAM), chitinase A1, integrin b-4 subunit, growth hormone receptor, erythropoietin receptor, prolactin receptor, interleukin-4 receptor a-chain, granulocyte colony-stimulating factor (GC-SF), interferon-g receptor, cytokine receptor, ciliary neurotrophic factor a, amongst others.

What InterPro Tells Us

P13726 Human Tissue Factor

InterPro Domain Architecture

InterPro Entry	Signatures	Graphical Match	Method Name
IPR000282	PS50299		CR2A
IPR000282	PS50300		CR2B
IPR001187	PF01108		Tissue_fac
IPR001187	PR00346		TISSUEFACTOR
IPR001187	PS00621		TISSUE_FACTOR
IPR008957	SSF49265		FN_III-like
Structural Features
1jps	1jpsT
2.60.40.30.1	2hft01
2.60.40.30.2	1boy02
b.1.2.1	d2hft_1
b.1.2.1	d2hft_2
Structural Predictions
MB_P13726

From the graphical match above, you can see that the signatures are grouped into three InterPro entries for human tissue factor. These entries give information about the domain architecture of the protein, as well as its family relationships.

To look at the family relationships, we need to consider entry IPR001187, which represents the Tissue Factor family of proteins, and which has three signatures: PF01108 from the PFAM database, PR00346 from the PRINTS database, and PS00621 from the PROSITE database (the PROSITE pattern uses the region of the protein centred on two conserved cysteines involved in the first disulphide bond).

The domain architecture of the extracellular region of human Tissue Factor consists of two domains, both with the same fibronectin type III fold. These domains have been classified by two InterPro entries. IPR000282 represents the cytokine receptor class II domains, and has two signatures: PS50299 and PS50300 from the PROSITE database. This entry groups together closely related proteins that share high sequence and structural identity. IPR008957 represents domains with a fibronectin type III-like fold, and which has one signature: SSF49265 from the SUPERFAMILY database. This entry groups together more distantly related proteins than those found in IPR000282, but which share the same immunoglobulin-like fibronectin-type structural fold, and which are believed to have a common ancestor.

The remaining six entries in the table above give information on the structure of this protein, the first five presenting known structural data from the structural database PDB (green stripe) and the structural classification databases CATH (pink stripe) and SCOP (black stripe) (the names such as 2hft01 are derived from the PDB entry upon which they are based, here PDB entry 2hft, chain O, fragment 1). The graphical match for the PDB entry 1jps displays the full length of the original PDB entry, here covering almost the entire protein. The CATH and SCOP entries breakdown the PDB data into its two constituent domains and provide a structural classification for each domain, in this case they have the same fibronectin type II-like fold (SCOP d2hft_1 and d2hft_2, and CATH 2hft01 and 1boy02).

The ‘Structural Predictions’ entry, MB_P13726 gives information on the predicted structure of this protein, and is from the homology model database ModBase (yellow stripe). Homology models are included for regions that have no known structure, here the N-terminal 30 amino acids of the protein.

What the Structure Tells Us

Structures associated with human Tissue Factor can be viewed using AstexViewer®, which is linked from the Match Table via the logo on the InterPro page (please note, there is no link directly from this page to the AstexViewer®, therefore you need to go to the link on the InterPro page for P13726). The AstexViewer® displays the PDB structure with the specific CATH or SCOP domain highlighted.

There are structures available for Tissue Factor from different species in the Protein Data Bank (PDB). A detailed description and visualisation of the structural features of Tissue Factor can be found at the PDB ‘Molecule of the Month’. The crystallographic structures of Tissue Factor proteins have provided insight into the mechanism of action of these important receptors.

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