Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P10646 (TFPI1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 179. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tissue factor pathway inhibitor

Short name=TFPI
Alternative name(s):
Extrinsic pathway inhibitor
Short name=EPI
Lipoprotein-associated coagulation inhibitor
Short name=LACI
Gene names
Name:TFPI
Synonyms:LACI, TFPI1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length304 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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.

Subcellular location

Isoform Alpha: Secreted Ref.18.

Isoform Beta: Microsome membrane; Lipid-anchorGPI-anchor Ref.18.

Tissue specificity

Mostly in endothelial cells.

Domain

This inhibitor contains three inhibitory domains. The first domain interacts with VIIa and TF, the second one with Xa.

Post-translational modification

O-glycosylated. Ref.10 Ref.14

Sequence similarities

Contains 3 BPTI/Kunitz inhibitor domains.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Alpha (identifier: P10646-1)

Also known as: TFPIalpha;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Beta (identifier: P10646-2)

Also known as: TFPIbeta;

The sequence of this isoform differs from the canonical sequence as follows:
     210-251: EFHGPSWCLT...CRPFKYSGCG → VTKEGTNDGW...LGLDSISCLC
     252-304: Missing.
Note: GPI-anchored.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Ref.10 Ref.11 Ref.12
Chain29 – 304276Tissue factor pathway inhibitor Ref.1
PRO_0000016871

Regions

Domain54 – 10451BPTI/Kunitz inhibitor 1
Domain125 – 17551BPTI/Kunitz inhibitor 2
Domain217 – 26751BPTI/Kunitz inhibitor 3

Sites

Site64 – 652Reactive bond
Site135 – 1362Reactive bond
Site227 – 2282Reactive bond
Site2561Not glycosylated

Amino acid modifications

Glycosylation421O-linked (GalNAc...); partial Ref.10
Glycosylation1451N-linked (GlcNAc...) Ref.10 Ref.14 Ref.16
Glycosylation1951N-linked (GlcNAc...) Ref.10 Ref.14
Glycosylation2021O-linked (GalNAc...); partial Ref.10 Ref.14
Glycosylation2031O-linked (GalNAc...) Ref.10 Ref.14
Disulfide bond54 ↔ 104 By similarity
Disulfide bond63 ↔ 87 By similarity
Disulfide bond79 ↔ 100 By similarity
Disulfide bond125 ↔ 175
Disulfide bond134 ↔ 158
Disulfide bond150 ↔ 171
Disulfide bond217 ↔ 267
Disulfide bond226 ↔ 250
Disulfide bond242 ↔ 263

Natural variations

Alternative sequence210 – 25142EFHGP…YSGCG → VTKEGTNDGWKNAAHIYQVF LNAFCIHASMFFLGLDSISC LC in isoform Beta.
VSP_003030
Alternative sequence252 – 30453Missing in isoform Beta.
VSP_003031
Natural variant2921V → M. Ref.22
Corresponds to variant rs5940 [ dbSNP | Ensembl ].
VAR_012004

Experimental info

Mutagenesis641K → I: Abolishes inhibition of VII(a)/TF.
Mutagenesis1351R → L: Abolishes inhibition of X(a).
Mutagenesis2271R → L: Abolishes inhibition of VII(a)/TF.

Secondary structure

........................................ 304
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha (TFPIalpha) [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: 5281E32B758B44FE

FASTA30435,015
        10         20         30         40         50         60 
MIYTMKKVHA LWASVCLLLN LAPAPLNADS EEDEEHTIIT DTELPPLKLM HSFCAFKADD 

        70         80         90        100        110        120 
GPCKAIMKRF FFNIFTRQCE EFIYGGCEGN QNRFESLEEC KKMCTRDNAN RIIKTTLQQE 

       130        140        150        160        170        180 
KPDFCFLEED PGICRGYITR YFYNNQTKQC ERFKYGGCLG NMNNFETLEE CKNICEDGPN 

       190        200        210        220        230        240 
GFQVDNYGTQ LNAVNNSLTP QSTKVPSLFE FHGPSWCLTP ADRGLCRANE NRFYYNSVIG 

       250        260        270        280        290        300 
KCRPFKYSGC GGNENNFTSK QECLRACKKG FIQRISKGGL IKTKRKRKKQ RVKIAYEEIF 


VKNM 

« Hide

Isoform Beta (TFPIbeta) [UniParc].

Checksum: 9B3F276A52B4F0B9
Show »

FASTA25128,653

References

« Hide 'large scale' references
[1]"Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains."
Wun T.-C., Kretzmer K.K., Girard T.J., Miletich J.P., Broze G.J. Jr.
J. Biol. Chem. 263:6001-6004(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
[2]"Identification of the 1.4 kb and 4.0 kb messages for the lipoprotein associated coagulation inhibitor and expression of the encoded protein."
Girard T.J., Warren L.A., Novotny W.F., Bejcek B.E., Miletich J.P., Broze G.J. Jr.
Thromb. Res. 55:37-50(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
[3]"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."
van der Logt C.P.E., Reitsma P.H., Bertina R.M.
Biochemistry 30:1571-1577(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA).
[4]"Structure of the human lipoprotein-associated coagulation inhibitor gene. Intro/exon gene organization and localization of the gene to chromosome 2."
Girard T.J., Eddy R., Wesselschmidt R.L., Macphail L.A., Likert K.M., Byers M.G., Shows T.B., Broze G.J. Jr.
J. Biol. Chem. 266:5036-5041(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA).
[5]Chang J.-Y., Monroe D.M., Roberts H.R.
Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA).
[6]SeattleSNPs variation discovery resource
Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , 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 E.A., 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 S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA).
Tissue: Pancreas.
[10]"Biochemical characterization of plasma-derived tissue factor pathway inhibitor: post-translational modification of free, full-length form with particular reference to the sugar chain."
Mori Y., Hamuro T., Nakashima T., Hamamoto T., Natsuka S., Hase S., Iwanaga S.
J. Thromb. Haemost. 7:111-120(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 29-304, IDENTIFICATION BY MASS SPECTROMETRY, GLYCOSYLATION AT THR-42; ASN-145; ASN-195; SER-202 AND THR-203.
[11]"Purification and characterization of the lipoprotein-associated coagulation inhibitor from human plasma."
Novotny W.F., Girard T.J., Miletich J.P., Broze G.J. Jr.
J. Biol. Chem. 264:18832-18837(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 29-50.
[12]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 29-43.
[13]"Functional significance of the Kunitz-type inhibitory domains of lipoprotein-associated coagulation inhibitor."
Girard T.J., Warren L.A., Novotny W.F., Likert K.M., Brown S.G., Miletich J.P., Broze G.J. Jr.
Nature 338:518-520(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: INHIBITORY SITES.
[14]"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."
Nakahara Y., Miyata T., Hamuro T., Funatsu A., Miyagi M., Tsunasawa S., Kato H.
Biochemistry 35:6450-6459(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-145; ASN-195; SER-202 AND THR-203.
[15]"Regulation of coagulation by a multivalent Kunitz-type inhibitor."
Broze G.J. Jr., Girard T.J., Novotny W.F.
Biochemistry 29:7539-7546(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[16]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-145.
Tissue: Plasma.
[17]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"TFPIbeta is the GPI-anchored TFPI isoform on human endothelial cells and placental microsomes."
Girard T.J., Tuley E., Broze G.J. Jr.
Blood 119:1256-1262(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION (ISOFORM BETA), GPI-ANCHOR.
[19]"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."
Stubbs M.T., Morenweiser R., Stuerzebecher J., Bauer M., Bode W., Huber R., Piechottka G.P., Matschiner G., Sommerhoff C.P., Fritz H., Auerswald E.A.
J. Biol. Chem. 272:19931-19937(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 121-178 IN COMPLEX WITH TRYPSIN.
[20]"The second Kunitz domain of human tissue factor pathway inhibitor: cloning, structure determination and interaction with factor Xa."
Burgering M.J.M., Orbons L.P.M., van der Doelen A., Mulders J., Theunissen H.J.M., Grootenhuis P.D.J., Bode W., Huber R., Stubbs M.T.
J. Mol. Biol. 269:395-407(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 121-182.
[21]"Structural mechanism for heparin-binding of the third Kunitz domain of human tissue factor pathway inhibitor."
Mine S., Yamazaki T., Miyata T., Hara S., Kato H.
Biochemistry 41:78-85(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 210-270.
[22]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MET-292.
[23]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J03225 mRNA. Translation: AAA52022.1.
M58650 expand/collapse EMBL AC list , M58644, M58645, M58646, M58647, M58648, M58649 Genomic DNA. Translation: AAA59480.1.
M59499 expand/collapse EMBL AC list , M59493, M59494, M59495, M59496, M59497, M59498 Genomic DNA. Translation: AAA59526.1.
AF021834 mRNA. Translation: AAD01700.1.
AY263365 Genomic DNA. Translation: AAO89075.1.
AC007319 Genomic DNA. Translation: AAY14807.1.
CH471058 Genomic DNA. Translation: EAX10921.1.
CH471058 Genomic DNA. Translation: EAX10922.1.
BC015514 mRNA. Translation: AAH15514.1.
PIRTIHUGK. A23712.
RefSeqNP_001027452.1. NM_001032281.2.
NP_006278.1. NM_006287.4.
XP_005246875.1. XM_005246818.1.
XP_005246876.1. XM_005246819.1.
XP_005246877.1. XM_005246820.1.
UniGeneHs.516578.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ADZNMR-A121-182[»]
1IRHNMR-A210-270[»]
1TFXX-ray2.60C/D121-178[»]
4BQDX-ray2.48A/B29-107[»]
4DTGX-ray1.80K119-178[»]
ProteinModelPortalP10646.
SMRP10646. Positions 51-270.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112893. 12 interactions.
STRING9606.ENSP00000233156.

Chemistry

DrugBankDB00036. Coagulation factor VIIa.

Protein family/group databases

MEROPSI02.950.

PTM databases

PhosphoSiteP10646.
UniCarbKBP10646.

Polymorphism databases

DMDM125932.

Proteomic databases

PaxDbP10646.
PeptideAtlasP10646.
PRIDEP10646.

Protocols and materials databases

DNASU7035.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000233156; ENSP00000233156; ENSG00000003436. [P10646-1]
ENST00000339091; ENSP00000342306; ENSG00000003436. [P10646-2]
ENST00000392365; ENSP00000376172; ENSG00000003436. [P10646-1]
ENST00000409676; ENSP00000386344; ENSG00000003436. [P10646-2]
GeneID7035.
KEGGhsa:7035.
UCSCuc002upy.3. human. [P10646-1]
uc002uqa.2. human. [P10646-2]

Organism-specific databases

CTD7035.
GeneCardsGC02M188328.
HGNCHGNC:11760. TFPI.
HPACAB020842.
HPA005575.
MIM152310. gene.
neXtProtNX_P10646.
PharmGKBPA36475.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG86404.
HOGENOMHOG000231818.
HOVERGENHBG056804.
InParanoidP10646.
KOK03909.
OMAFIQRISK.
OrthoDBEOG73FQKT.
PhylomeDBP10646.
TreeFamTF315349.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.

Gene expression databases

ArrayExpressP10646.
BgeeP10646.
CleanExHS_TFPI.
GenevestigatorP10646.

Family and domain databases

Gene3D4.10.410.10. 3 hits.
InterProIPR002223. Prot_inh_Kunz-m.
IPR008296. Prot_inhib_I2_TFPI.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view]
PfamPF00014. Kunitz_BPTI. 3 hits.
[Graphical view]
PIRSFPIRSF001620. TFPI. 1 hit.
PRINTSPR00759. BASICPTASE.
SMARTSM00131. KU. 3 hits.
[Graphical view]
SUPFAMSSF57362. SSF57362. 3 hits.
PROSITEPS00280. BPTI_KUNITZ_1. 3 hits.
PS50279. BPTI_KUNITZ_2. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTFPI. human.
EvolutionaryTraceP10646.
GeneWikiTissue_factor_pathway_inhibitor.
GenomeRNAi7035.
NextBio27483.
PMAP-CutDBP10646.
PROP10646.
SOURCESearch...

Entry information

Entry nameTFPI1_HUMAN
AccessionPrimary (citable) accession number: P10646
Secondary accession number(s): O95103, Q53TS4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: April 16, 2014
This is version 179 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM