Tissue factor pathway inhibitor (or TFPI) is a single-chain polypeptide which can reversibly inhibit Factor Xa (Xa) and Thrombin

Thrombin

Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...

 (Factor IIa). While Xa is inhibited, the Xa-TFPI complex can subsequently also inhibit the FVIIa

Factor VII

Factor VII is one of the proteins that causes blood to clot in the coagulation cascade. It is an enzyme of the serine protease class. A recombinant form of human factor VIIa has U.S. Food and Drug Administration approval for uncontrolled bleeding in hemophilia patients...

-tissue factor

Tissue factor

Tissue factor, also called platelet tissue factor, factor III, thrombokinase, or CD142 is a protein present in subendothelial tissue, platelets, and leukocytes necessary for the initiation of thrombin formation from the zymogen prothrombin. An incorrect synonym is thromboplastin...

 complex.
TFPI contributes significantly to the inhibition of Xa in vivo, despite being present at concentrations of only 2.5 nM.

Genetics

The gene for TFPI is located on chromosome 2q31-q32.1, and has nine exons which span 70 kb. The gene has not been completely sequenced yet. A similar gene, termed TFPI2, has been identified on chromosome 7q22; in addition to TFPI activity, its product also has retinal pigment epithelial cell growth-promoting properties.

Protein structure

TFPI has a relative molecular mass of 34,000 to 40,000 depending on the degree of proteolysis of the C-terminal region.

TFPI consists of a highly negatively-charged amino-terminus, three tandemly-linked Kunitz domain

Kunitz domain

Kunitz domains are the active domains of proteins that inhibit the function of protein degrading enzymes or, more specifically, domains of Kunitz-type protease inhibitors. They are relatively small with a length of about 50 to 60 amino acids and a molecular weight of 6 kDa...

s, and a highly positively-charged carboxy-terminus. With its Kunitz domains, TFPI exhibits significant homology with human inter-alpha-trypsin inhibitor

Inter-alpha-trypsin inhibitor

Inter-alpha-trypsin inhibitors are plasma proteins consisting of three of four heavy chains selected from the group ITIH1, ITIH2, ITIH3, ITIH4 and one light chain selected from the group AMBP or SPINT2. They function as protease inhibitors....

 and bovine basic pancreatic trypsin inhibitor.

Interactions

Tissue factor pathway inhibitor has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with Factor X

Factor X

Factor X, also known by the eponym Stuart-Prower factor or as prothrombinase, is an enzyme of the coagulation cascade. It is a serine endopeptidase .-Physiology:...

.

Further reading