Tissue factor pathway inhibitor

Tissue factor pathway inhibitor

Tissue factor pathway inhibitor (or TFPI) is a single-chain polypeptide which can reversibly inhibit Factor Xa (Xa). While Xa is inhibited, the Xa-TFPI complex can subsequently also inhibit the FVIIa-TF complex.TFPI contributes significantly to the inhibition of Xa in vivo, despite being present at concentrations of only 2.5nM.

Genetics

The gene for TFPI is located on chromosome 2q31-q32.1, and has nine exons which span 70kb. 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 34000 to 40000 depending on the degree of proteolysis of the C-terminal region.

ee also

* hemostasis

External links

* ("TFPI1"), OMIM|600033 ("TFPI2")

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Broze GJ, Girard TJ, Novotny WF |title=Regulation of coagulation by a multivalent Kunitz-type inhibitor. |journal=Biochemistry |volume=29 |issue= 33 |pages= 7539–46 |year= 1991 |pmid= 2271516 |doi=
*cite journal | author=McVey JH |title=Tissue factor pathway. |journal=Baillieres Best Pract. Res. Clin. Haematol. |volume=12 |issue= 3 |pages= 361–72 |year= 2000 |pmid= 10856975 |doi=
*cite journal | author=Bajaj MS, Birktoft JJ, Steer SA, Bajaj SP |title=Structure and biology of tissue factor pathway inhibitor. |journal=Thromb. Haemost. |volume=86 |issue= 4 |pages= 959–72 |year= 2002 |pmid= 11686353 |doi=
*cite journal | author=Witt I |title= [Tissue factor pathway inhibitor: biochemistry, molecular biology, physiology and physiopathology] |journal=Hamostaseologie |volume=22 |issue= 2 |pages= 30–5 |year= 2002 |pmid= 12193974 |doi= 10.1267/Hamo02020071 |doi_brokendate=2008-06-24
*cite journal | author=Lwaleed BA, Bass PS |title=Tissue factor pathway inhibitor: structure, biology and involvement in disease. |journal=J. Pathol. |volume=208 |issue= 3 |pages= 327–39 |year= 2006 |pmid= 16261634 |doi= 10.1002/path.1871
*cite journal | author=Van der Logt CP, Kluck PM, Wiegant J, "et al." |title=Refined regional assignment of the human tissue factor pathway inhibitor (TFPI) gene to chromosome band 2q32 by non-isotopic in situ hybridization. |journal=Hum. Genet. |volume=89 |issue= 5 |pages= 577–8 |year= 1992 |pmid= 1353057 |doi=
*cite journal | author=Higuchi DA, Wun TC, Likert KM, Broze GJ |title=The effect of leukocyte elastase on tissue factor pathway inhibitor. |journal=Blood |volume=79 |issue= 7 |pages= 1712–9 |year= 1992 |pmid= 1558967 |doi=
*cite journal | author=van der Logt CP, Reitsma PH, Bertina RM |title=Intron-exon organization of the human gene coding for the lipoprotein-associated coagulation inhibitor: the factor Xa dependent inhibitor of the extrinsic pathway of coagulation. |journal=Biochemistry |volume=30 |issue= 6 |pages= 1571–7 |year= 1991 |pmid= 1993173 |doi=
*cite journal | author=Girard TJ, Eddy R, Wesselschmidt RL, "et al." |title=Structure of the human lipoprotein-associated coagulation inhibitor gene. Intro/exon gene organization and localization of the gene to chromosome 2. |journal=J. Biol. Chem. |volume=266 |issue= 8 |pages= 5036–41 |year= 1991 |pmid= 2002045 |doi=
*cite journal | author=Wun TC, Kretzmer KK, Girard TJ, "et al." |title=Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains. |journal=J. Biol. Chem. |volume=263 |issue= 13 |pages= 6001–4 |year= 1988 |pmid= 2452157 |doi=
*cite journal | author=Novotny WF, Girard TJ, Miletich JP, Broze GJ |title=Purification and characterization of the lipoprotein-associated coagulation inhibitor from human plasma. |journal=J. Biol. Chem. |volume=264 |issue= 31 |pages= 18832–7 |year= 1989 |pmid= 2553722 |doi=
*cite journal | author=Girard TJ, Warren LA, Novotny WF, "et al." |title=Identification of the 1.4 kb and 4.0 kb messages for the lipoprotein associated coagulation inhibitor and expression of the encoded protein. |journal=Thromb. Res. |volume=55 |issue= 1 |pages= 37–50 |year= 1989 |pmid= 2781520 |doi=
*cite journal | author=Girard TJ, Warren LA, Novotny WF, "et al." |title=Functional significance of the Kunitz-type inhibitory domains of lipoprotein-associated coagulation inhibitor. |journal=Nature |volume=338 |issue= 6215 |pages= 518–20 |year= 1989 |pmid= 2927510 |doi= 10.1038/338518a0
*cite journal | author=Broze GJ, Miletich JP |title=Characterization of the inhibition of tissue factor in serum. |journal=Blood |volume=69 |issue= 1 |pages= 150–5 |year= 1987 |pmid= 3024756 |doi=
*cite journal | author=Broze GJ, Warren LA, Novotny WF, "et al." |title=The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action. |journal=Blood |volume=71 |issue= 2 |pages= 335–43 |year= 1988 |pmid= 3422166 |doi=
*cite journal | author=Rao LV, Rapaport SI |title=Studies of a mechanism inhibiting the initiation of the extrinsic pathway of coagulation. |journal=Blood |volume=69 |issue= 2 |pages= 645–51 |year= 1987 |pmid= 3492226 |doi=
*cite journal | author=Stubbs MT, Huber R, Bode W |title=Crystal structures of factor Xa specific inhibitors in complex with trypsin: structural grounds for inhibition of factor Xa and selectivity against thrombin. |journal=FEBS Lett. |volume=375 |issue= 1-2 |pages= 103–7 |year= 1996 |pmid= 7498454 |doi=
*cite journal | author=Warshawsky I, Bu G, Mast A, "et al." |title=The carboxy terminus of tissue factor pathway inhibitor is required for interacting with hepatoma cells in vitro and in vivo. |journal=J. Clin. Invest. |volume=95 |issue= 4 |pages= 1773–81 |year= 1995 |pmid= 7706485 |doi=
*cite journal | author=Broze GJ, Lange GW, Duffin KL, MacPhail L |title=Heterogeneity of plasma tissue factor pathway inhibitor. |journal=Blood Coagul. Fibrinolysis |volume=5 |issue= 4 |pages= 551–9 |year= 1995 |pmid= 7841311 |doi=

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