Biology:Tissue factor pathway inhibitor

Short description: Single-chain polypeptide capable of inhibiting blood clotting Factor Xa

Generic protein structure example

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.

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, has been identified on chromosome 7, at 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 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.

See also

• Hemostasis

External links

• Online Mendelian Inheritance in Man (OMIM) 152310 (TFPI1), Online Mendelian Inheritance in Man (OMIM) 600033 (TFPI2)
• Overview of all the structural information available in the PDB for UniProt: P10646 (Tissue factor pathway inhibitor) at the PDBe-KB.

Further reading

• "Regulation of coagulation by a multivalent Kunitz-type inhibitor.". Biochemistry 29 (33): 7539–46. 1991. 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. 
• "Structure and biology of tissue factor pathway inhibitor.". Thromb. Haemost. 86 (4): 959–72. 2002. PMID 11686353. 
• Witt I (2002). "Tissue-factor-pathway-Inhibitor: Biochemie, Molekularbiologie, Physiologie und Pathophysiologie". Hamostaseologie 22 (2): 30–5. doi:10.1055/s-0037-1619536. PMID 12193974. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0037-1619536. 
• "Tissue factor pathway inhibitor: structure, biology and involvement in disease.". J. Pathol. 208 (3): 327–39. 2006. doi:10.1002/path.1871. PMID 16261634. 
• "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. 1992. doi:10.1007/bf00219189. PMID 1353057. 
• "The effect of leukocyte elastase on tissue factor pathway inhibitor.". Blood 79 (7): 1712–9. 1992. doi:10.1182/blood.V79.7.1712.1712. PMID 1558967. 
• "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. 1991. doi:10.1021/bi00220a018. PMID 1993173. 
• "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. 1991. doi:10.1016/S0021-9258(19)67752-5. PMID 2002045. 
• "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. 1988. doi:10.1016/S0021-9258(18)68737-X. PMID 2452157. 
• "Purification and characterization of the lipoprotein-associated coagulation inhibitor from human plasma.". J. Biol. Chem. 264 (31): 18832–7. 1989. doi:10.1016/S0021-9258(18)51542-8. PMID 2553722. 
• "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. 1989. doi:10.1016/0049-3848(89)90454-4. PMID 2781520. 
• "Functional significance of the Kunitz-type inhibitory domains of lipoprotein-associated coagulation inhibitor.". Nature 338 (6215): 518–20. 1989. doi:10.1038/338518a0. PMID 2927510. Bibcode: 1989Natur.338..518G. 
• "Characterization of the inhibition of tissue factor in serum.". Blood 69 (1): 150–5. 1987. doi:10.1182/blood.V69.1.150.150. PMID 3024756. 
• "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. 1988. doi:10.1182/blood.V71.2.335.335. PMID 3422166. 
• "Studies of a mechanism inhibiting the initiation of the extrinsic pathway of coagulation.". Blood 69 (2): 645–51. 1987. doi:10.1182/blood.V69.2.645.645. PMID 3492226. 
• "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. 1996. doi:10.1016/0014-5793(95)01190-P. PMID 7498454. 
• "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. 1995. doi:10.1172/JCI117855. PMID 7706485. 
• "Heterogeneity of plasma tissue factor pathway inhibitor.". Blood Coagul. Fibrinolysis 5 (4): 551–9. 1995. PMID 7841311.