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Tissue factor pathway inhibitor - Revision history
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*{{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 }}</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*{{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 }}</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>*{{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= }}</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>*{{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= <ins style="font-weight: bold; text-decoration: none;">10.1053/beha.1999.0030</ins>}}</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*{{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 |doi= }}</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*{{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 |doi= }}</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*{{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}}</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*{{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}}</div></td></tr>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*{{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 }}</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*{{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 }}</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>*{{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 }}</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>*{{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 <ins style="font-weight: bold; text-decoration: none;">|bibcode=1989Natur.338..518G </ins>}}</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*{{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= }}</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*{{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= }}</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*{{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= }}</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>*{{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= }}</div></td></tr>
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<p><b>New page</b></p><div>{{PBB_Controls<br />
| update_page = yes <br />
| require_manual_inspection = no <br />
| update_protein_box = yes<br />
| update_summary = no<br />
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}}<br />
{{GNF_Protein_box<br />
| image = PBB_Protein_TFPI_image.jpg<br />
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1adz.<br />
| Name = Tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor)<br />
| HGNCid = 11760<br />
| Symbol = TFPI<br />
| AltSymbols =; TFI; EPI; LACI<br />
| OMIM = 152310<br />
| ECnumber = <br />
| Homologene = 4579<br />
| MGIid = 1095418<br />
| GeneAtlas_image1 = PBB_GE_TFPI_209676_at_tn.png<br />
| GeneAtlas_image2 = PBB_GE_TFPI_210664_s_at_tn.png<br />
| GeneAtlas_image3 = PBB_GE_TFPI_210665_at_tn.png<br />
| Function = {{GNF_GO|id=GO:0004867 |text = serine-type endopeptidase inhibitor activity}} {{GNF_GO|id=GO:0030414 |text = protease inhibitor activity}} <br />
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} <br />
| Process = {{GNF_GO|id=GO:0007596 |text = blood coagulation}} <br />
| Orthologs = {{GNF_Ortholog_box<br />
| Hs_EntrezGene = 7035<br />
| Hs_Ensembl = ENSG00000003436<br />
| Hs_RefseqProtein = NP_001027452<br />
| Hs_RefseqmRNA = NM_001032281<br />
| Hs_GenLoc_db = <br />
| Hs_GenLoc_chr = 2<br />
| Hs_GenLoc_start = 188039530<br />
| Hs_GenLoc_end = 188127410<br />
| Hs_Uniprot = P10646<br />
| Mm_EntrezGene = 21788<br />
| Mm_Ensembl = ENSMUSG00000027082<br />
| Mm_RefseqmRNA = NM_011576<br />
| Mm_RefseqProtein = NP_035706<br />
| Mm_GenLoc_db = <br />
| Mm_GenLoc_chr = 2<br />
| Mm_GenLoc_start = 84233699<br />
| Mm_GenLoc_end = 84275013<br />
| Mm_Uniprot = O54819<br />
}}<br />
}}<br />
{{SI}}<br />
{{CMG}}<br />
<br />
<br />
<br />
'''Tissue factor pathway inhibitor''' (or '''TFPI''') is a single-chain polypeptide which can reversibly inhibit [[Factor X]]a (Xa). While Xa is inhibited, the Xa-TFPI complex can subsequently also inhibit the [[Factor VII|FVIIa]]-[[tissue factor|TF]] complex.<br />
TFPI contributes significantly to the inhibition of Xa in vivo, despite being present at concentrations of only 2.5nM.<br />
<br />
==Genetics==<br />
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.<br />
<br />
==Protein structure==<br />
TFPI has a relative molecular mass of 34000 to 40000 depending on the degree of proteolysis of the C-terminal region.<br />
<br />
==See also==<br />
* [[hemostasis]]<br />
<br />
==External links==<br />
* {{OMIM|152310}} (''TFPI1''), {{OMIM|600033}} (''TFPI2'')<br />
<br />
==References==<br />
{{reflist}}<br />
==Further reading==<br />
{{refbegin | 2}}<br />
{{PBB_Further_reading <br />
| citations = <br />
*{{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= }}<br />
*{{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= }}<br />
*{{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= }}<br />
*{{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 }}<br />
*{{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 }}<br />
*{{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= }}<br />
*{{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= }}<br />
*{{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= }}<br />
*{{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= }}<br />
*{{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= }}<br />
*{{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= }}<br />
*{{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= }}<br />
*{{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 }}<br />
*{{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= }}<br />
*{{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= }}<br />
*{{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= }}<br />
*{{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= }}<br />
*{{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= }}<br />
*{{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= }}<br />
}}<br />
{{refend}}<br />
<br />
{{Coagulation}}<br />
<br />
[[Category:Coagulation system]]<br />
[[Category:Hematology]]<br />
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