TFPI1_HUMAN
ID TFPI1_HUMAN Reviewed; 304 AA.
AC P10646; O95103; Q53TS4;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 241.
DE RecName: Full=Tissue factor pathway inhibitor;
DE Short=TFPI;
DE AltName: Full=Extrinsic pathway inhibitor;
DE Short=EPI;
DE AltName: Full=Lipoprotein-associated coagulation inhibitor;
DE Short=LACI;
DE Flags: Precursor;
GN Name=TFPI; Synonyms=LACI, TFPI1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
RX PubMed=2452157; DOI=10.1016/s0021-9258(18)68737-x;
RA Wun T.-C., Kretzmer K.K., Girard T.J., Miletich J.P., Broze G.J. Jr.;
RT "Cloning and characterization of a cDNA coding for the lipoprotein-
RT associated coagulation inhibitor shows that it consists of three tandem
RT Kunitz-type inhibitory domains.";
RL J. Biol. Chem. 263:6001-6004(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
RX PubMed=2781520; DOI=10.1016/0049-3848(89)90454-4;
RA Girard T.J., Warren L.A., Novotny W.F., Bejcek B.E., Miletich J.P.,
RA Broze G.J. Jr.;
RT "Identification of the 1.4 kb and 4.0 kb messages for the lipoprotein
RT associated coagulation inhibitor and expression of the encoded protein.";
RL Thromb. Res. 55:37-50(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA).
RX PubMed=1993173; DOI=10.1021/bi00220a018;
RA van der Logt C.P.E., Reitsma P.H., Bertina R.M.;
RT "Intron-exon organization of the human gene coding for the lipoprotein-
RT associated coagulation inhibitor: the factor Xa dependent inhibitor of the
RT extrinsic pathway of coagulation.";
RL Biochemistry 30:1571-1577(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA).
RX PubMed=2002045; DOI=10.1016/s0021-9258(19)67752-5;
RA Girard T.J., Eddy R., Wesselschmidt R.L., Macphail L.A., Likert K.M.,
RA Byers M.G., Shows T.B., Broze G.J. Jr.;
RT "Structure of the human lipoprotein-associated coagulation inhibitor gene.
RT Intro/exon gene organization and localization of the gene to chromosome
RT 2.";
RL J. Biol. Chem. 266:5036-5041(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA).
RA Chang J.-Y., Monroe D.M., Roberts H.R.;
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 29-304, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP GLYCOSYLATION AT THR-42; ASN-145; ASN-195; SER-202 AND THR-203.
RX PubMed=19017259; DOI=10.1111/j.1538-7836.2008.03222.x;
RA Mori Y., Hamuro T., Nakashima T., Hamamoto T., Natsuka S., Hase S.,
RA Iwanaga S.;
RT "Biochemical characterization of plasma-derived tissue factor pathway
RT inhibitor: post-translational modification of free, full-length form with
RT particular reference to the sugar chain.";
RL J. Thromb. Haemost. 7:111-120(2009).
RN [11]
RP PROTEIN SEQUENCE OF 29-50.
RX PubMed=2553722; DOI=10.1016/s0021-9258(18)51542-8;
RA Novotny W.F., Girard T.J., Miletich J.P., Broze G.J. Jr.;
RT "Purification and characterization of the lipoprotein-associated
RT coagulation inhibitor from human plasma.";
RL J. Biol. Chem. 264:18832-18837(1989).
RN [12]
RP PROTEIN SEQUENCE OF 29-43.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [13]
RP INHIBITORY SITES.
RX PubMed=2927510; DOI=10.1038/338518a0;
RA Girard T.J., Warren L.A., Novotny W.F., Likert K.M., Brown S.G.,
RA Miletich J.P., Broze G.J. Jr.;
RT "Functional significance of the Kunitz-type inhibitory domains of
RT lipoprotein-associated coagulation inhibitor.";
RL Nature 338:518-520(1989).
RN [14]
RP GLYCOSYLATION AT ASN-145; ASN-195; SER-202 AND THR-203.
RX PubMed=8639592; DOI=10.1021/bi9524880;
RA Nakahara Y., Miyata T., Hamuro T., Funatsu A., Miyagi M., Tsunasawa S.,
RA Kato H.;
RT "Amino acid sequence and carbohydrate structure of a recombinant human
RT tissue factor pathway inhibitor expressed in Chinese hamster ovary cells:
RT one N- and two O-linked carbohydrate chains are located between Kunitz
RT domains 2 and 3 and one N-linked carbohydrate chain is in Kunitz domain
RT 2.";
RL Biochemistry 35:6450-6459(1996).
RN [15]
RP REVIEW.
RX PubMed=2271516; DOI=10.1021/bi00485a001;
RA Broze G.J. Jr., Girard T.J., Novotny W.F.;
RT "Regulation of coagulation by a multivalent Kunitz-type inhibitor.";
RL Biochemistry 29:7539-7546(1990).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-145.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP SUBCELLULAR LOCATION (ISOFORM BETA), AND GPI-ANCHOR.
RX PubMed=22144186; DOI=10.1182/blood-2011-10-388512;
RA Girard T.J., Tuley E., Broze G.J. Jr.;
RT "TFPIbeta is the GPI-anchored TFPI isoform on human endothelial cells and
RT placental microsomes.";
RL Blood 119:1256-1262(2012).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 121-178 IN COMPLEX WITH TRYPSIN.
RX PubMed=9242660; DOI=10.1074/jbc.272.32.19931;
RA Stubbs M.T., Morenweiser R., Stuerzebecher J., Bauer M., Bode W., Huber R.,
RA Piechottka G.P., Matschiner G., Sommerhoff C.P., Fritz H., Auerswald E.A.;
RT "The three-dimensional structure of recombinant leech-derived tryptase
RT inhibitor in complex with trypsin. Implications for the structure of human
RT mast cell tryptase and its inhibition.";
RL J. Biol. Chem. 272:19931-19937(1997).
RN [20]
RP STRUCTURE BY NMR OF 121-182.
RX PubMed=9199408; DOI=10.1006/jmbi.1997.1029;
RA Burgering M.J.M., Orbons L.P.M., van der Doelen A., Mulders J.,
RA Theunissen H.J.M., Grootenhuis P.D.J., Bode W., Huber R., Stubbs M.T.;
RT "The second Kunitz domain of human tissue factor pathway inhibitor:
RT cloning, structure determination and interaction with factor Xa.";
RL J. Mol. Biol. 269:395-407(1997).
RN [21]
RP STRUCTURE BY NMR OF 210-270.
RX PubMed=11772005; DOI=10.1021/bi011299g;
RA Mine S., Yamazaki T., Miyata T., Hara S., Kato H.;
RT "Structural mechanism for heparin-binding of the third Kunitz domain of
RT human tissue factor pathway inhibitor.";
RL Biochemistry 41:78-85(2002).
RN [22]
RP VARIANT MET-292.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [23]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
CC -!- FUNCTION: Inhibits factor X (X(a)) directly and, in a Xa-dependent way,
CC inhibits VIIa/tissue factor activity, presumably by forming a
CC quaternary Xa/LACI/VIIa/TF complex. It possesses an antithrombotic
CC action and also the ability to associate with lipoproteins in plasma.
CC -!- SUBCELLULAR LOCATION: [Isoform Alpha]: Secreted.
CC -!- SUBCELLULAR LOCATION: [Isoform Beta]: Microsome membrane
CC {ECO:0000269|PubMed:22144186}; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:22144186}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha; Synonyms=TFPIalpha;
CC IsoId=P10646-1; Sequence=Displayed;
CC Name=Beta; Synonyms=TFPIbeta;
CC IsoId=P10646-2; Sequence=VSP_003030, VSP_003031;
CC -!- TISSUE SPECIFICITY: Mostly in endothelial cells.
CC -!- DOMAIN: This inhibitor contains three inhibitory domains. The first
CC domain interacts with VIIa and TF, the second one with Xa.
CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:16335952,
CC ECO:0000269|PubMed:19017259, ECO:0000269|PubMed:8639592}.
CC -!- MISCELLANEOUS: [Isoform Beta]: GPI-anchored. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=TFPI entry;
CC URL="https://en.wikipedia.org/wiki/TFPI";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/tfpi/";
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DR EMBL; J03225; AAA52022.1; -; mRNA.
DR EMBL; M58650; AAA59480.1; -; Genomic_DNA.
DR EMBL; M58644; AAA59480.1; JOINED; Genomic_DNA.
DR EMBL; M58645; AAA59480.1; JOINED; Genomic_DNA.
DR EMBL; M58646; AAA59480.1; JOINED; Genomic_DNA.
DR EMBL; M58647; AAA59480.1; JOINED; Genomic_DNA.
DR EMBL; M58648; AAA59480.1; JOINED; Genomic_DNA.
DR EMBL; M58649; AAA59480.1; JOINED; Genomic_DNA.
DR EMBL; M59499; AAA59526.1; -; Genomic_DNA.
DR EMBL; M59493; AAA59526.1; JOINED; Genomic_DNA.
DR EMBL; M59494; AAA59526.1; JOINED; Genomic_DNA.
DR EMBL; M59495; AAA59526.1; JOINED; Genomic_DNA.
DR EMBL; M59496; AAA59526.1; JOINED; Genomic_DNA.
DR EMBL; M59497; AAA59526.1; JOINED; Genomic_DNA.
DR EMBL; M59498; AAA59526.1; JOINED; Genomic_DNA.
DR EMBL; AF021834; AAD01700.1; -; mRNA.
DR EMBL; AY263365; AAO89075.1; -; Genomic_DNA.
DR EMBL; AC007319; AAY14807.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX10921.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX10922.1; -; Genomic_DNA.
DR EMBL; BC015514; AAH15514.1; -; mRNA.
DR CCDS; CCDS2294.1; -. [P10646-1]
DR CCDS; CCDS33349.1; -. [P10646-2]
DR PIR; A23712; TIHUGK.
DR RefSeq; NP_001027452.1; NM_001032281.3. [P10646-2]
DR RefSeq; NP_001305870.1; NM_001318941.2. [P10646-2]
DR RefSeq; NP_001316168.1; NM_001329239.1. [P10646-1]
DR RefSeq; NP_001316169.1; NM_001329240.1. [P10646-1]
DR RefSeq; NP_001316170.1; NM_001329241.1. [P10646-1]
DR RefSeq; NP_006278.1; NM_006287.5. [P10646-1]
DR RefSeq; XP_005246876.1; XM_005246819.1.
DR RefSeq; XP_006712783.1; XM_006712720.3. [P10646-1]
DR RefSeq; XP_011510011.1; XM_011511709.2. [P10646-1]
DR PDB; 1ADZ; NMR; -; A=118-182.
DR PDB; 1IRH; NMR; -; A=210-270.
DR PDB; 1TFX; X-ray; 2.60 A; C/D=121-178.
DR PDB; 4BQD; X-ray; 2.48 A; A/B=29-107.
DR PDB; 4DTG; X-ray; 1.80 A; K=119-178.
DR PDB; 5NMV; X-ray; 1.65 A; K=29-107.
DR PDB; 6BX8; X-ray; 1.98 A; B/D/F/H=50-107.
DR PDB; 7V1N; EM; 3.20 A; K=1-209.
DR PDBsum; 1ADZ; -.
DR PDBsum; 1IRH; -.
DR PDBsum; 1TFX; -.
DR PDBsum; 4BQD; -.
DR PDBsum; 4DTG; -.
DR PDBsum; 5NMV; -.
DR PDBsum; 6BX8; -.
DR PDBsum; 7V1N; -.
DR AlphaFoldDB; P10646; -.
DR SMR; P10646; -.
DR BioGRID; 112893; 19.
DR CORUM; P10646; -.
DR IntAct; P10646; 2.
DR STRING; 9606.ENSP00000233156; -.
DR ChEMBL; CHEMBL3713062; -.
DR DrugBank; DB14562; Andexanet alfa.
DR DrugBank; DB00036; Coagulation factor VIIa Recombinant Human.
DR DrugBank; DB06779; Dalteparin.
DR MEROPS; I02.011; -.
DR MEROPS; I02.012; -.
DR MEROPS; I02.950; -.
DR GlyConnect; 602; 12 N-Linked glycans, 1 O-Linked glycan.
DR GlyGen; P10646; 6 sites, 20 N-linked glycans (3 sites), 4 O-linked glycans (4 sites).
DR iPTMnet; P10646; -.
DR PhosphoSitePlus; P10646; -.
DR BioMuta; TFPI; -.
DR DMDM; 125932; -.
DR CPTAC; non-CPTAC-1163; -.
DR EPD; P10646; -.
DR jPOST; P10646; -.
DR MassIVE; P10646; -.
DR MaxQB; P10646; -.
DR PaxDb; P10646; -.
DR PeptideAtlas; P10646; -.
DR PRIDE; P10646; -.
DR ProteomicsDB; 52636; -. [P10646-1]
DR ProteomicsDB; 52637; -. [P10646-2]
DR ABCD; P10646; 47 sequenced antibodies.
DR Antibodypedia; 790; 734 antibodies from 41 providers.
DR DNASU; 7035; -.
DR Ensembl; ENST00000233156.9; ENSP00000233156.3; ENSG00000003436.16. [P10646-1]
DR Ensembl; ENST00000339091.8; ENSP00000342306.4; ENSG00000003436.16. [P10646-2]
DR Ensembl; ENST00000392365.5; ENSP00000376172.1; ENSG00000003436.16. [P10646-1]
DR Ensembl; ENST00000409676.5; ENSP00000386344.1; ENSG00000003436.16. [P10646-2]
DR GeneID; 7035; -.
DR KEGG; hsa:7035; -.
DR MANE-Select; ENST00000233156.9; ENSP00000233156.3; NM_006287.6; NP_006278.1.
DR UCSC; uc002upy.4; human. [P10646-1]
DR CTD; 7035; -.
DR DisGeNET; 7035; -.
DR GeneCards; TFPI; -.
DR HGNC; HGNC:11760; TFPI.
DR HPA; ENSG00000003436; Tissue enhanced (liver, placenta).
DR MIM; 152310; gene.
DR neXtProt; NX_P10646; -.
DR OpenTargets; ENSG00000003436; -.
DR PharmGKB; PA36475; -.
DR VEuPathDB; HostDB:ENSG00000003436; -.
DR eggNOG; KOG4295; Eukaryota.
DR GeneTree; ENSGT00940000160767; -.
DR InParanoid; P10646; -.
DR OMA; CALKDEP; -.
DR OrthoDB; 1009074at2759; -.
DR PhylomeDB; P10646; -.
DR TreeFam; TF315349; -.
DR PathwayCommons; P10646; -.
DR Reactome; R-HSA-140834; Extrinsic Pathway of Fibrin Clot Formation.
DR SignaLink; P10646; -.
DR SIGNOR; P10646; -.
DR BioGRID-ORCS; 7035; 17 hits in 1083 CRISPR screens.
DR ChiTaRS; TFPI; human.
DR EvolutionaryTrace; P10646; -.
DR GeneWiki; Tissue_factor_pathway_inhibitor; -.
DR GenomeRNAi; 7035; -.
DR Pharos; P10646; Tchem.
DR PRO; PR:P10646; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P10646; protein.
DR Bgee; ENSG00000003436; Expressed in right lung and 178 other tissues.
DR ExpressionAtlas; P10646; baseline and differential.
DR Genevisible; P10646; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005901; C:caveola; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0007596; P:blood coagulation; TAS:ProtInc.
DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; IEP:UniProtKB.
DR GO; GO:0030195; P:negative regulation of blood coagulation; IDA:UniProtKB.
DR CDD; cd00109; KU; 3.
DR Gene3D; 4.10.410.10; -; 3.
DR InterPro; IPR002223; Kunitz_BPTI.
DR InterPro; IPR036880; Kunitz_BPTI_sf.
DR InterPro; IPR020901; Prtase_inh_Kunz-CS.
DR InterPro; IPR008296; TFPI-like.
DR Pfam; PF00014; Kunitz_BPTI; 3.
DR PIRSF; PIRSF001620; TFPI; 1.
DR PRINTS; PR00759; BASICPTASE.
DR SMART; SM00131; KU; 3.
DR SUPFAM; SSF57362; SSF57362; 3.
DR PROSITE; PS00280; BPTI_KUNITZ_1; 3.
DR PROSITE; PS50279; BPTI_KUNITZ_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Blood coagulation;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW Glycoprotein; GPI-anchor; Hemostasis; Lipoprotein; Membrane; Microsome;
KW Protease inhibitor; Reference proteome; Repeat; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..28
FT /evidence="ECO:0000269|PubMed:15340161,
FT ECO:0000269|PubMed:19017259, ECO:0000269|PubMed:2553722"
FT CHAIN 29..304
FT /note="Tissue factor pathway inhibitor"
FT /evidence="ECO:0000269|PubMed:2452157"
FT /id="PRO_0000016871"
FT DOMAIN 54..104
FT /note="BPTI/Kunitz inhibitor 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DOMAIN 125..175
FT /note="BPTI/Kunitz inhibitor 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DOMAIN 217..267
FT /note="BPTI/Kunitz inhibitor 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT SITE 64..65
FT /note="Reactive bond"
FT SITE 135..136
FT /note="Reactive bond"
FT SITE 227..228
FT /note="Reactive bond"
FT SITE 256
FT /note="Not glycosylated"
FT CARBOHYD 42
FT /note="O-linked (GalNAc...) threonine; partial"
FT /evidence="ECO:0000269|PubMed:19017259"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19017259, ECO:0000269|PubMed:8639592"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19017259,
FT ECO:0000269|PubMed:8639592"
FT CARBOHYD 202
FT /note="O-linked (GalNAc...) serine; partial"
FT /evidence="ECO:0000269|PubMed:19017259,
FT ECO:0000269|PubMed:8639592"
FT CARBOHYD 203
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:19017259,
FT ECO:0000269|PubMed:8639592"
FT DISULFID 54..104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 63..87
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 79..100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 125..175
FT DISULFID 134..158
FT DISULFID 150..171
FT DISULFID 217..267
FT DISULFID 226..250
FT DISULFID 242..263
FT VAR_SEQ 210..251
FT /note="EFHGPSWCLTPADRGLCRANENRFYYNSVIGKCRPFKYSGCG -> VTKEGT
FT NDGWKNAAHIYQVFLNAFCIHASMFFLGLDSISCLC (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.5"
FT /id="VSP_003030"
FT VAR_SEQ 252..304
FT /note="Missing (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.5"
FT /id="VSP_003031"
FT VARIANT 292
FT /note="V -> M (in dbSNP:rs5940)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_012004"
FT MUTAGEN 64
FT /note="K->I: Abolishes inhibition of VII(a)/TF."
FT MUTAGEN 135
FT /note="R->L: Abolishes inhibition of X(a)."
FT MUTAGEN 227
FT /note="R->L: Abolishes inhibition of VII(a)/TF."
FT STRAND 31..39
FT /evidence="ECO:0007829|PDB:4BQD"
FT HELIX 51..55
FT /evidence="ECO:0007829|PDB:5NMV"
FT STRAND 67..73
FT /evidence="ECO:0007829|PDB:5NMV"
FT TURN 74..77
FT /evidence="ECO:0007829|PDB:5NMV"
FT STRAND 78..84
FT /evidence="ECO:0007829|PDB:5NMV"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:6BX8"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:5NMV"
FT HELIX 97..104
FT /evidence="ECO:0007829|PDB:5NMV"
FT STRAND 112..115
FT /evidence="ECO:0007829|PDB:1ADZ"
FT HELIX 123..126
FT /evidence="ECO:0007829|PDB:4DTG"
FT STRAND 138..144
FT /evidence="ECO:0007829|PDB:4DTG"
FT TURN 145..148
FT /evidence="ECO:0007829|PDB:4DTG"
FT STRAND 149..155
FT /evidence="ECO:0007829|PDB:4DTG"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:4DTG"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:4DTG"
FT HELIX 168..175
FT /evidence="ECO:0007829|PDB:4DTG"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:1ADZ"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:1IRH"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:1IRH"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:1IRH"
FT TURN 237..239
FT /evidence="ECO:0007829|PDB:1IRH"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:1IRH"
FT STRAND 257..260
FT /evidence="ECO:0007829|PDB:1IRH"
FT HELIX 261..267
FT /evidence="ECO:0007829|PDB:1IRH"
SQ SEQUENCE 304 AA; 35015 MW; 5281E32B758B44FE CRC64;
MIYTMKKVHA LWASVCLLLN LAPAPLNADS EEDEEHTIIT DTELPPLKLM HSFCAFKADD
GPCKAIMKRF FFNIFTRQCE EFIYGGCEGN QNRFESLEEC KKMCTRDNAN RIIKTTLQQE
KPDFCFLEED PGICRGYITR YFYNNQTKQC ERFKYGGCLG NMNNFETLEE CKNICEDGPN
GFQVDNYGTQ LNAVNNSLTP QSTKVPSLFE FHGPSWCLTP ADRGLCRANE NRFYYNSVIG
KCRPFKYSGC GGNENNFTSK QECLRACKKG FIQRISKGGL IKTKRKRKKQ RVKIAYEEIF
VKNM
