Tissue factor pathway inhibitor

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Tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor)
PBB Protein TFPI image.jpg
PDB rendering based on 1adz.
Identifiers
Symbol(s) TFPI; TFI; EPI; LACI
External IDs OMIM: 152310 MGI1095418 Homologene4579
RNA expression pattern

PBB GE TFPI 209676 at tn.png

PBB GE TFPI 210664 s at tn.png

PBB GE TFPI 210665 at tn.png

More reference expression data

Orthologs
Human Mouse
Entrez 7035 21788
Ensembl ENSG00000003436 ENSMUSG00000027082
Uniprot P10646 O54819
Refseq NM_001032281 (mRNA)
NP_001027452 (protein)
NM_011576 (mRNA)
NP_035706 (protein)
Location Chr 2: 188.04 - 188.13 Mb Chr 2: 84.23 - 84.28 Mb
Pubmed search [1] [2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]


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.

See also

External links

References

Further reading

  • Broze GJ, Girard TJ, Novotny WF (1991). "Regulation of coagulation by a multivalent Kunitz-type inhibitor.". Biochemistry. 29 (33): 7539–46. PMID 2271516. 
  • McVey JH (2000). "Tissue factor pathway.". Baillieres Best Pract. Res. Clin. Haematol. 12 (3): 361–72. 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. PMID 12193974. doi:10.1267/Hamo02020071. 
  • Lwaleed BA, Bass PS (2006). "Tissue factor pathway inhibitor: structure, biology and involvement in disease.". J. Pathol. 208 (3): 327–39. PMID 16261634. doi:10.1002/path.1871. 
  • 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. 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. 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. 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. PMID 2927510. doi:10.1038/338518a0. 
  • 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. 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. 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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