View source for Tissue factor pathway inhibitor

{{Short description|Single-chain polypeptide capable of inhibiting blood clotting Factor Xa}}
{{Infobox_gene}}
'''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 [[Factor VII|FVIIa]]-[[tissue factor]] complex.
TFPI contributes significantly to the inhibition of Xa in vivo, despite being present at concentrations of only 2.5&nbsp;nM.

==Genetics==
The gene for TFPI is located on chromosome 2q31-q32.1, and has nine exons which span 70&nbsp;kb. A similar gene, termed ''[[TFPI2]]'', has been identified on [[chromosome 7]], at [[Locus (genetics)|locus]] 7q21.3; 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]]s, and a highly positively charged carboxy-terminus. With its Kunitz domains, TFPI exhibits significant homology with human [[inter-alpha-trypsin inhibitor]] and bovine [[basic pancreatic trypsin inhibitor]].

==Interactions==
Tissue factor pathway inhibitor has been shown to [[Protein-protein interaction|interact]] with [[Factor X]].<ref name=pmid3422166>{{cite journal |last=Broze |first=G J |author2=Warren L A |author3=Novotny W F |author4=Higuchi D A |author5=Girard J J |author6=Miletich J P  |date=Feb 1988 |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 |location = UNITED STATES| issn = 0006-4971| pmid = 3422166 |doi=10.1182/blood.V71.2.335.335 |doi-access=free }}</ref>

==See also==
* [[Hemostasis]]

==References==
{{reflist}}

==External links==
* {{OMIM|152310}} (''TFPI1''), {{OMIM|600033}} (''TFPI2'')
* {{PDBe-KB2|P10646|Tissue factor pathway inhibitor}}

==Further reading==
{{refbegin | 2}}
*{{cite journal  |vauthors=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=10.1021/bi00485a001  }}
*{{cite journal  | author=McVey JH |title=Tissue factor pathway. |journal=Best Practice & Research. Clinical Haematology |volume=12 |issue= 3 |pages= 361–72 |year= 2000 |pmid= 10856975 |doi=  10.1053/beha.1999.0030}}
*{{cite journal  |vauthors=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 }}
*{{cite journal  | author=Witt I |title=Tissue-factor-pathway-Inhibitor: Biochemie, Molekularbiologie, Physiologie und Pathophysiologie
|trans-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=10.1055/s-0037-1619536|s2cid=73349573
|url=https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0037-1619536 |url-access=subscription }}
*{{cite journal  |vauthors=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 |s2cid=26710725 }}
*{{cite journal   |vauthors=Van der Logt CP, Kluck PM, Wiegant J, etal |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=  10.1007/bf00219189|s2cid=5722297 }}
*{{cite journal  |vauthors=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=  10.1182/blood.V79.7.1712.1712|doi-access=free }}
*{{cite journal  |vauthors=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=10.1021/bi00220a018  }}
*{{cite journal   |vauthors=Girard TJ, Eddy R, Wesselschmidt RL, etal |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 |doi=10.1016/S0021-9258(19)67752-5 |pmid= 2002045 |doi-access=free }}
*{{cite journal   |vauthors=Wun TC, Kretzmer KK, Girard TJ, etal |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 |doi=10.1016/S0021-9258(18)68737-X |pmid= 2452157 |doi-access=free }}
*{{cite journal  |vauthors=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 |doi=10.1016/S0021-9258(18)51542-8 |pmid= 2553722 |doi-access=free }}
*{{cite journal   |vauthors=Girard TJ, Warren LA, Novotny WF, etal |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=10.1016/0049-3848(89)90454-4  }}
*{{cite journal   |vauthors=Girard TJ, Warren LA, Novotny WF, etal |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 |bibcode=1989Natur.338..518G |s2cid=4255627 }}
*{{cite journal  |vauthors=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=  10.1182/blood.V69.1.150.150|doi-access=free }}
*{{cite journal   |vauthors=Broze GJ, Warren LA, Novotny WF, etal |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=  10.1182/blood.V71.2.335.335|doi-access=free }}
*{{cite journal  |vauthors=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=  10.1182/blood.V69.2.645.645|doi-access=free }}
*{{cite journal  |vauthors=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=10.1016/0014-5793(95)01190-P  |s2cid=1779098 |doi-access=free }}
*{{cite journal   |vauthors=Warshawsky I, Bu G, Mast A, etal |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=10.1172/JCI117855  | pmc=295702  }}
*{{cite journal  |vauthors=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 }}
{{refend}}
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[[Category:Coagulation system]]

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