Tissue factor pathway inhibitor

Details

Name
Tissue factor pathway inhibitor
Synonyms
  • EPI
  • Extrinsic pathway inhibitor
  • LACI
  • Lipoprotein-associated coagulation inhibitor
  • TFPI
  • TFPI1
Gene Name
TFPI
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001925|Tissue factor pathway inhibitor
MIYTMKKVHALWASVCLLLNLAPAPLNADSEEDEEHTIITDTELPPLKLMHSFCAFKADD
GPCKAIMKRFFFNIFTRQCEEFIYGGCEGNQNRFESLEECKKMCTRDNANRIIKTTLQQE
KPDFCFLEEDPGICRGYITRYFYNNQTKQCERFKYGGCLGNMNNFETLEECKNICEDGPN
GFQVDNYGTQLNAVNNSLTPQSTKVPSLFEFHGPSWCLTPADRGLCRANENRFYYNSVIG
KCRPFKYSGCGGNENNFTSKQECLRACKKGFIQRISKGGLIKTKRKRKKQRVKIAYEEIF
VKNM
Number of residues
304
Molecular Weight
35014.835
Theoretical pI
8.31
GO Classification
Functions
endopeptidase inhibitor activity / serine-type endopeptidase inhibitor activity
Processes
blood coagulation / blood coagulation, extrinsic pathway / negative regulation of endopeptidase activity
Components
anchored component of membrane / cell surface / endoplasmic reticulum / extracellular region / extracellular space / organelle membrane / plasma membrane
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Inhibits factor X (X(a)) directly and, in a Xa-dependent way, inhibits VIIa/tissue factor activity, presumably by forming a quaternary Xa/LACI/VIIa/TF complex. It possesses an antithrombotic action and also the ability to associate with lipoproteins in plasma.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0010679|Tissue factor pathway inhibitor (TFPI)
ATGATTTACACAATGAAGAAAGTACATGCACTTTGGGCTTCTGTATGCCTGCTGCTTAAT
CTTGCCCCTGCCCCTCTTAATGCTGATTCTGAGGAAGATGAAGAACACACAATTATCACA
GATACGGAGTTGCCACCACTGAAACTTATGCATTCATTTTGTGCATTCAAGGCGGATGAT
GGCCCATGTAAAGCAATCATGAAAAGATTTTTCTTCAATATTTTCACTCGACAGTGCGAA
GAATTTATATATGGGGGATGTGAAGGAAATCAGAATCGATTTGAAAGTCTGGAAGAGTGC
AAAAAAATGTGTACAAGAGATAATGCAAACAGGATTATAAAGACAACATTGCAACAAGAA
AAGCCAGATTTCTGCTTTTTGGAAGAAGATCCTGGAATATGTCGAGGTTATATTACCAGG
TATTTTTATAACAATCAGACAAAACAGTGTGAACGTTTCAAGTATGGTGGATGCCTGGGC
AATATGAACAATTTTGAGACACTGGAAGAATGCAAGAACATTTGTGAAGATGGTCCGAAT
GGTTTCCAGGTGGATAATTATGGAACCCAGCTCAATGCTGTGAATAACTCCCTGACTCCG
CAATCAACCAAGGTTCCCAGCCTTTTTGTTACAAAAGAAGGAACAAATGATGGTTGGAAG
AATGCGGCTCATATTTACCAAGTCTTTCTGAACGCCTTCTGCATTCATGCATCCATGTTC
TTTCTAGGATTGGATAGCATTTCATGCCTATGTTAA
Chromosome Location
2
Locus
2q32
External Identifiers
ResourceLink
UniProtKB IDP10646
UniProtKB Entry NameTFPI1_HUMAN
GenBank Protein ID180546
GenBank Gene IDJ03225
GenAtlas IDTFPI
HGNC IDHGNC:11760
General References
  1. Wun TC, Kretzmer KK, Girard TJ, Miletich JP, Broze GJ Jr: 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. 1988 May 5;263(13):6001-4. [Article]
  2. Girard TJ, Warren LA, Novotny WF, Bejcek BE, Miletich JP, Broze GJ Jr: 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. 1989 Jul 1;55(1):37-50. [Article]
  3. van der Logt CP, Reitsma PH, Bertina RM: 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. 1991 Feb 12;30(6):1571-7. [Article]
  4. Girard TJ, Eddy R, Wesselschmidt RL, MacPhail LA, Likert KM, Byers MG, Shows TB, Broze GJ Jr: Structure of the human lipoprotein-associated coagulation inhibitor gene. Intro/exon gene organization and localization of the gene to chromosome 2. J Biol Chem. 1991 Mar 15;266(8):5036-41. [Article]
  5. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [Article]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. Mori Y, Hamuro T, Nakashima T, Hamamoto T, Natsuka S, Hase S, Iwanaga S: Biochemical characterization of plasma-derived tissue factor pathway inhibitor: post-translational modification of free, full-length form with particular reference to the sugar chain. J Thromb Haemost. 2009 Jan;7(1):111-20. doi: 10.1111/j.1538-7836.2008.03222.x. Epub 2008 Nov 11. [Article]
  8. Novotny WF, Girard TJ, Miletich JP, Broze GJ Jr: Purification and characterization of the lipoprotein-associated coagulation inhibitor from human plasma. J Biol Chem. 1989 Nov 5;264(31):18832-7. [Article]
  9. Zhang Z, Henzel WJ: Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Sci. 2004 Oct;13(10):2819-24. Epub 2004 Aug 31. [Article]
  10. Girard TJ, Warren LA, Novotny WF, Likert KM, Brown SG, Miletich JP, Broze GJ Jr: Functional significance of the Kunitz-type inhibitory domains of lipoprotein-associated coagulation inhibitor. Nature. 1989 Apr 6;338(6215):518-20. [Article]
  11. Nakahara Y, Miyata T, Hamuro T, Funatsu A, Miyagi M, Tsunasawa S, Kato H: Amino acid sequence and carbohydrate structure of a recombinant human tissue factor pathway inhibitor expressed in Chinese hamster ovary cells: one N-and two O-linked carbohydrate chains are located between Kunitz domains 2 and 3 and one N-linked carbohydrate chain is in Kunitz domain 2. Biochemistry. 1996 May 21;35(20):6450-9. [Article]
  12. Broze GJ Jr, Girard TJ, Novotny WF: Regulation of coagulation by a multivalent Kunitz-type inhibitor. Biochemistry. 1990 Aug 21;29(33):7539-46. [Article]
  13. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. [Article]
  14. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  15. Girard TJ, Tuley E, Broze GJ Jr: TFPIbeta is the GPI-anchored TFPI isoform on human endothelial cells and placental microsomes. Blood. 2012 Feb 2;119(5):1256-62. doi: 10.1182/blood-2011-10-388512. Epub 2011 Dec 5. [Article]
  16. Stubbs MT, Morenweiser R, Sturzebecher J, Bauer M, Bode W, Huber R, Piechottka GP, Matschiner G, Sommerhoff CP, Fritz H, Auerswald EA: The three-dimensional structure of recombinant leech-derived tryptase inhibitor in complex with trypsin. Implications for the structure of human mast cell tryptase and its inhibition. J Biol Chem. 1997 Aug 8;272(32):19931-7. [Article]
  17. Burgering MJ, Orbons LP, van der Doelen A, Mulders J, Theunissen HJ, Grootenhuis PD, Bode W, Huber R, Stubbs MT: The second Kunitz domain of human tissue factor pathway inhibitor: cloning, structure determination and interaction with factor Xa. J Mol Biol. 1997 Jun 13;269(3):395-407. [Article]
  18. Mine S, Yamazaki T, Miyata T, Hara S, Kato H: Structural mechanism for heparin-binding of the third Kunitz domain of human tissue factor pathway inhibitor. Biochemistry. 2002 Jan 8;41(1):78-85. [Article]
  19. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00036Coagulation factor VIIa Recombinant HumanapprovedunknownDetails
DB06779DalteparinapprovedyesinhibitorDetails
DB14562Andexanet alfaapproved, investigationalyesinhibitorDetails