CD142 F3 (coagulation factor III, thromboplastin, tissue factor), TF (tissue factor)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Astrocyte
Keratinocyte
Epithelial Cell
Schwann Cell
Stromal Cell
Monocyte
Endothelial Cell
Fibroblast
Cytokine
Liver
Pancreas
Spleen
Thyroid
Blood vessel
Syncytiotrophoblast
45 / 45
47 / 47

Expression
CD142 is expressed at high levels on epidermal keratinocytes, glomerular epithelial cells and various other epithelia, adventitial cells of blood vessels, astrocytes, myocardium, Schwann cells of peripheral nerves and stromal cells of organs such as liver, pancreas, spleen and thyroid.  Normally CD142 is absent from all cells in direct contact with plasma.  CD142 can be induced by various inflammatory mediators on monocytes and vascular endothelial cells by inflammatory mediators.  In cultured fibroblasts, CD142 is inducible by serum and cytokines.



Structure
MOLECULAR FAMILY NAME: Belongs to the class II cytokine receptor family.

CD142 is a single-chain, type-1 glycoprotein.  It contains a 32 aa leader sequence, a 219 aa extracellular domain which contains 2 fibronectin type-3 domains related to cytokine receptors, a 23 aa hydrophobic transmembrane domain and a 21 aa cytoplasmic domain.
 
MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Many cell types 45-47 kDa 45-47 kDa

POST-TRANSCRIPTIONAL MODIFICATION

There is a single 2.3 kb mRNA species in many cell types.  In some cell types like monocytes, there is an additional mRNA species in which the 1st intron has not been removed, but is apparently not translated. Half-life of mRNA is short in <2 hours and variable.

POST-TRANSLATIONAL MODIFICATION

There is a single chain protein with no proteolytic cleavage required for activation.  There are 3 N-linked carbohydrate chains which are dispensable for function and a phosphorylated cytoplasmic region.  The cytoplasmic cysteine residue is thioester linked to fatty acyl chain.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD142
Molecule Comment
Factor VIIa
Factor Xa/TFPI Binds to (and inhibits) the complex of CD142 and factor VIIa



Function
CD142 encodes a coagulation factor III which enables cells to initate the blood coagulation cascades and propagation.  It functions in normal hemostasis, is a component of the cellular immune response and it functions as the high-affinity receptor for the coagulation factor VII.  The resulting complex provides a catalytic event that is responsible for the initiation of the coagulation protease cascades by specific limited proteolysis.  Unlike the other factors of these protease cascades, which circulate as nonfunctional orecursors, this factor is a potent initiator that is fully functional when expressed on cell surfaces.  CD142 can be induced by inflammatory mediators.  Expression on cell surface confers a procoagulant phenotype.  There is an initial report that binding of factor VIIa to CD142 results in changes in intracellular calcium ion levels.

BIOCHEMICAL ACTIVITY

The 1:1 complex of CD142 and factor VIIa is the enzyme that initiates the blood clotting cascade.  Factor VIIa, a serine protease, is the catalytic subunit, and CD142 is the essential regulatory subunit.  CD142 also binds zymogen factor VII, the inactive precursor form.  Once bound, a variety of serine proteases rapidly activate factor VII and VIIa via limited proteolysis.

DISEASE RELEVANCE AND FUNCTION OF CD142 IN INTACT ANIMAL

CD142 is the major initiator of the blood clotting cascade in normal hemostasis and many if not all thrombotic diseases but may be a therapeutic target in the treatment and prevention of thrombosis.  The CD142 gene knockout in mice is embryonically lethal and is associated with severe bleeding and defects in cardiovascular development.  Inappropriate expression of CD142 may play a role in tumor biology promoting metastasis and angiogenesis.  Antibodies to CD142 protect animals against lethality of septic shock.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD142
Molecule Comment
Ap-1
c-Rel/p65
Egr-1
Sp1
Ets

SUBSTRATES
Molecule Comment
Factor X Activated via limited proteolysis by the cell-surface complex of CD142 and factor VIIa
Factor IX Activated via limited proteolysis by the cell-surface complex of CD142 and factor VIIa
Factor VII Activated via limited proteolysis by the cell-surface complex of CD142 and factor VIIa

ENZYMES WHICH MODIFY CD142: No information.

ADDITIONAL INSIGHTS

Recent reports have implicated CD142 as also playing roles in tumor metastasis, breast cancer, hyperplasia and angiogenesis.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 2152P13726
Antibodies

Revised June 25, 2008


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