• F3 [HUGO gene name]
• coagulation Factor III
• thromboplastin
• tissue factor, TF

MAJOR LINKS FOR CD142  

• NCBI LocusLink Record: 2152
• Mendelian Inheritance in Man (OMIM): 134390
• SwissProt annotated protein record: P13726

• 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 to VIIa via limited proteolysis

CELLULAR FUNCTION OF CD142  

• 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

DISEASE RELEVANCE OF CD142 AND FUNCTION OF CD142 IN INTACT ANIMAL  

• CD142 is the major initiator of clotting in normal hemostasis and many (if not all) thrombotic diseases
• Gene knockout in mice is embryonically lethal and associated with severe bleeding and defects in cardiovascular development
• Antibodies to CD142 protect animals against lethality of septic shock

• Families in which CD142 is a member
  • CD142-->serine protease cofactor

MOLECULAR STRUCTURE OF CD142  

• Single chain, type I transmembrane protein (263 amino acids)
• Extracellular region (219 amino acids) composed of two fibronectin type III domains (related to cytokine receptors). X-ray crystal structure solved
• Transmembrane domain (23 amino acids)
• Short cytoplasmic region (21 amino acids)

MOLECULAR MASS OF CD142  

POST-TRANSCRIPTIONAL MODIFICATION OF CD142  

• Single 2.3 kb mRNA species in many cell types
• In some cell types (e.g. monocytes) there is an additional mRNA species in which the first intron has not been removed, but this is apparently not translated
• Half-life of mRNA is short (<2 hr) and variable

POST-TRANSLATIONAL MODIFICATION OF CD142  

• Single-chain protein; no proteolytic cleavage required for activation
• Three N-linked carbohydrate chains (dispensable for function)
• Phosphorylated cytoplasmic region
• Cytoplasmic cysteine residue is thioester linked to a fatty acyl chain

SUBSTRATES FOR CD142  

ENZYMES WHICH MODIFY CD142   - No information

LIGANDS FOR CD142 AND MOLECULES ASSOCIATED WITH CD142  

• Expressed at high levels in 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 absent from all cells in direct contact with plasma
• CD 142 can be induced by various inflammatory mediators in monocytes and vascular endothelial cells
• In cultured fibroblasts, inducible by serum and cytokines

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

SELECTION OF OTHER CD142-SPECIFIC REFERENCE MAB   - No information

REVIEWS

1. Carson SD,Brozna JP The role of tissue factor in the production of thrombin. Blood Coagul Fibrinolysis 1993 4:281 PubMed

2. Mackman N Regulation of the tissue factor gene. FASEB J 1995 9:883 PubMed

PRIMARY CITATIONS

3. Albrecht S,Luther T,Grossmann H,Flossel C,Kotzsch M,Muller M An ELISA for tissue factor using monoclonal antibodies. Blood Coagul Fibrinolysis 1992 3:263 PubMed

4. Carson SD,Ross SE,Bach R,Guha A An inhibitory monoclonal antibody against human tissue factor. Blood 1987 70:490 PubMed

5. Morrissey JH,Fair DS,Edgington TS Monoclonal antibody analysis of purified and cell-associated tissue factor. Thromb Res 1988 52:247 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov