Tissue factor pathway inhibitor (or TFPI) is a single-chain polypeptide which can reversibly inhibit
factor Xa
Coagulation factor X (), or Stuart factor, is an enzyme of the coagulation cascade, encoded in humans by ''F10'' gene. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for ...
(Xa). While Xa is inhibited, the Xa-TFPI complex can subsequently also inhibit the
FVIIa-
tissue factor
Tissue factor, also called platelet tissue factor or Coagulation factor III, is a protein present in subendothelial tissue and leukocytes which plays a major role in coagulation and, in humans, is encoded by ''F3'' gene. Its role in the blood c ...
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. A similar gene, termed ''
TFPI2
Tissue factor pathway inhibitor 2 is a protein that in humans is encoded by the ''TFPI2'' gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DN ...
'', has been identified on
chromosome 7
Chromosome 7 is one of the 23 pairs of chromosomes in humans, who normally have two copies of this chromosome. Chromosome 7 spans about 160 million base pairs (the building material of DNA) and represents between 5 and 5.5 percent of the total DN ...
, at
locus 7q21.3; in addition to TFPI activity, its product also has
retinal pigment epithelial
The pigmented layer of retina or retinal pigment epithelium (RPE) is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells, and is firmly attached to the underlying choroid and overlying retinal visual ...
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 domains are the active protein domain, domains of proteins that inhibit the function of protease, protein degrading enzymes or, more specifically, domains of Kunitz-type are Protease inhibitor (biology), protease inhibitors. They are relat ...
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 inhibitors (IαI) 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 inhibit ...
and bovine
basic pancreatic trypsin inhibitor
The drug aprotinin (Trasylol, previously Bayer and now Nordic Group pharmaceuticals), is a small protein bovine pancreatic trypsin inhibitor (BPTI), or basic trypsin inhibitor of bovine pancreas, which is an antifibrinolytic molecule that inhibit ...
.
Interactions
Tissue factor pathway inhibitor has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with
Factor X
Coagulation factor X (), or Stuart factor, is an enzyme of the coagulation cascade, encoded in humans by ''F10'' gene. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for i ...
.
See also
*
Hemostasis
In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. Hemostasis involves three ...
References
External links
* (''TFPI1''), (''TFPI2'')
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Further reading
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Coagulation system
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