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-tissue factor complex.
TFPI contributes significantly to the inhibition of Xa in vivo, despite being present at concentrations of only 2.5 nM.
Contents
1Genetics
2Protein structure
3Interactions
4See also
5References
6External links
7Further reading
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 domains, 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 interact with Factor X.[5]
See also
Hemostasis
References
^ abcGRCh38: Ensembl release 89: ENSG00000003436 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000027082 - Ensembl, May 2017
^"Human PubMed Reference:".
^"Mouse PubMed Reference:".
^Broze, G J; Warren L A; Novotny W F; Higuchi D A; Girard J J; Miletich J P (Feb 1988). "The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action". Blood. UNITED STATES. 71 (2): 335–43. ISSN 0006-4971. PMID 3422166.
External links
Online Mendelian Inheritance in Man (OMIM) 152310 (TFPI1), Online Mendelian Inheritance in Man (OMIM) 600033 (TFPI2)
Further reading
Broze GJ, Girard TJ, Novotny WF (1991). "Regulation of coagulation by a multivalent Kunitz-type inhibitor". Biochemistry. 29 (33): 7539–46. doi:10.1021/bi00485a001. PMID 2271516.
McVey JH (2000). "Tissue factor pathway". Best Practice & Research. Clinical Haematology. 12 (3): 361–72. doi:10.1053/beha.1999.0030. PMID 10856975.
Bajaj MS, Birktoft JJ, Steer SA, Bajaj SP (2002). "Structure and biology of tissue factor pathway inhibitor". Thromb. Haemost. 86 (4): 959–72. PMID 11686353.
Witt I (2002). "[Tissue factor pathway inhibitor: biochemistry, molecular biology, physiology and physiopathology]". Hamostaseologie. 22 (2): 30–5. doi:10.1267/Hamo02020071. PMID 12193974.
Lwaleed BA, Bass PS (2006). "Tissue factor pathway inhibitor: structure, biology and involvement in disease". J. Pathol. 208 (3): 327–39. doi:10.1002/path.1871. PMID 16261634.
Van der Logt CP, Kluck PM, Wiegant J, et al. (1992). "Refined regional assignment of the human tissue factor pathway inhibitor (TFPI) gene to chromosome band 2q32 by non-isotopic in situ hybridization". Hum. Genet. 89 (5): 577–8. doi:10.1007/bf00219189. PMID 1353057.
Higuchi DA, Wun TC, Likert KM, Broze GJ (1992). "The effect of leukocyte elastase on tissue factor pathway inhibitor". Blood. 79 (7): 1712–9. PMID 1558967.
van der Logt CP, Reitsma PH, Bertina RM (1991). "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". Biochemistry. 30 (6): 1571–7. doi:10.1021/bi00220a018. PMID 1993173.
Girard TJ, Eddy R, Wesselschmidt RL, et al. (1991). "Structure of the human lipoprotein-associated coagulation inhibitor gene. Intro/exon gene organization and localization of the gene to chromosome 2". J. Biol. Chem. 266 (8): 5036–41. PMID 2002045.
Wun TC, Kretzmer KK, Girard TJ, et al. (1988). "Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains". J. Biol. Chem. 263 (13): 6001–4. PMID 2452157.
Novotny WF, Girard TJ, Miletich JP, Broze GJ (1989). "Purification and characterization of the lipoprotein-associated coagulation inhibitor from human plasma". J. Biol. Chem. 264 (31): 18832–7. PMID 2553722.
Girard TJ, Warren LA, Novotny WF, et al. (1989). "Identification of the 1.4 kb and 4.0 kb messages for the lipoprotein associated coagulation inhibitor and expression of the encoded protein". Thromb. Res. 55 (1): 37–50. doi:10.1016/0049-3848(89)90454-4. PMID 2781520.
Girard TJ, Warren LA, Novotny WF, et al. (1989). "Functional significance of the Kunitz-type inhibitory domains of lipoprotein-associated coagulation inhibitor". Nature. 338 (6215): 518–20. Bibcode:1989Natur.338..518G. doi:10.1038/338518a0. PMID 2927510.
Broze GJ, Miletich JP (1987). "Characterization of the inhibition of tissue factor in serum". Blood. 69 (1): 150–5. PMID 3024756.
Broze GJ, Warren LA, Novotny WF, et al. (1988). "The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action". Blood. 71 (2): 335–43. PMID 3422166.
Rao LV, Rapaport SI (1987). "Studies of a mechanism inhibiting the initiation of the extrinsic pathway of coagulation". Blood. 69 (2): 645–51. PMID 3492226.
Stubbs MT, Huber R, Bode W (1996). "Crystal structures of factor Xa specific inhibitors in complex with trypsin: structural grounds for inhibition of factor Xa and selectivity against thrombin". FEBS Lett. 375 (1–2): 103–7. doi:10.1016/0014-5793(95)01190-P. PMID 7498454.
Warshawsky I, Bu G, Mast A, et al. (1995). "The carboxy terminus of tissue factor pathway inhibitor is required for interacting with hepatoma cells in vitro and in vivo". J. Clin. Invest. 95 (4): 1773–81. doi:10.1172/JCI117855. PMC 295702. PMID 7706485.
Broze GJ, Lange GW, Duffin KL, MacPhail L (1995). "Heterogeneity of plasma tissue factor pathway inhibitor". Blood Coagul. Fibrinolysis. 5 (4): 551–9. PMID 7841311.
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PDB gallery
1adz: THE SOLUTION STRUCTURE OF THE SECOND KUNITZ DOMAIN OF TISSUE FACTOR PATHWAY INHIBITOR, NMR, 30 STRUCTURES
1irh: The Solution Structure of The Third Kunitz Domain of Tissue Factor Pathway Inhibitor
1tfx: COMPLEX OF THE SECOND KUNITZ DOMAIN OF TISSUE FACTOR PATHWAY INHIBITOR WITH PORCINE TRYPSIN
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Proteins involved in coagulation
Coagulation factors
Primary hemostasis
vWF
platelet membrane glycoproteins: Ib (A
B
IX)
IIb/IIIa (IIb
IIIa)
VI
Intrinsic pathway
HMWK/Bradykinin
Prekallikrein/Kallikrein
XII "Hageman"
XI
IX
VIII
Extrinsic pathway
III "Tissue factor"
VII
Common pathway
X
V
II "(Pro)thrombin"
I "Fibrin"
Fibrinogen (FGA, FGG)
XIII
Coagulation inhibitors
Antithrombin (inhibits II, IX, X, XI, XII)
Protein C (inhibits V, VIII)/Protein S (cofactor for protein C)
Protein Z (inhibits X)
ZPI (inhibits X, XI)
TFPI (inhibits III)
Thrombolysis/fibrinolysis
Plasmin
tPA/urokinase
PAI-1/2
α2-AP
α2-macroglobulin
TAFI
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…factor pathway inhibitor (TFPI) Contact activation pathway – C1 esterase inhibitor (C1-inh) TFPI circulates in plasma, but at very low concentrations, in contrast to AT . TFPI is a Kunitz-type protease …
…plasma and monocyte surface-associated tissue factor pathway inhibitor (TFPI)-1, which results from proteolysis by plasmin . TFPI-1 inhibits tissue factor-mediated activation of the coagulation pathway…
…kininogen, and coagulation factors VII, VIIa, and XII . Coexistent tissue factor pathway inhibitor (TFPI) and protein C immunoglobulin G (IgG) Ab, irrespective of their avidity, may be a useful marker for…
…early reduction in tissue factor pathway inhibitor (TFPI), which also favors fibrin deposition . This early response is followed by enhancement of TFPI expression in later stage disease, chronically inhibiting …
…independently of the tissue factor-factor VIIa pathway, which is shut down by tissue factor pathway inhibitor (TFPI) once the extrinsic pathway is activated. To counterbalance these procoagulant changes, the fibrinolytic …
English Journal
Transcription factor FOXP3: A repressor of the TFPI gene?
Skretting G, Andersen E, Myklebust CF, Sandset PM, Tinholt M, Iversen N, Stavik B.
Journal of cellular biochemistry. 2019 Aug;120(8)12924-12936.
Single nucleotide polymorphisms (SNPs) may play an important role in the risk of certain diseases. We have previously shown that the -287T/C SNP of the tissue factor pathway inhibitor (TFPI) gene promoter region exerts differential impact on TFPI mRNA expression; the C allele being associated with h
Factors Associated with Low Admission Platelet Count in Adults with Acute Aortic Dissection.
Li S, Lu J, Cheng W, Zhu J, Jin M.
Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia. 2019 Jun;25(3)142-148.
Platelets are crucial components of the coagulation processes, and low admission platelet count (PLC) is associated with adverse clinical outcomes in patients with Stanford type A acute aortic dissection (AAD). A total of 130 consecutive patients undergoing Stanford type A AAD surgery in Beijing Anz
Tissue factor (TF)-dependent coagulation contributes to lung inflammation and the pathogenesis of acute lung injury (ALI). In this study, we explored the roles of targeted endothelial anticoagulation in ALI using two strains of transgenic mice expressing either a membrane-tethered human tissue facto
Complete information for TFPI gene (Protein Coding), Tissue Factor Pathway Inhibitor, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium ... A. gosspyii yeast ...
Dellinger RP, Levy MM, Carlet JM, et al: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36:296-327.
