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Protein

Tissue factor pathway inhibitor

Gene

TFPI

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei64 – 65Reactive bond2
Sitei135 – 136Reactive bond2
Sitei227 – 228Reactive bond2

GO - Molecular functioni

  • endopeptidase inhibitor activity Source: ProtInc
  • serine-type endopeptidase inhibitor activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionProtease inhibitor, Serine protease inhibitor
Biological processBlood coagulation, Hemostasis

Enzyme and pathway databases

ReactomeiR-HSA-140834 Extrinsic Pathway of Fibrin Clot Formation
SIGNORiP10646

Protein family/group databases

MEROPSiI02.950

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:TFPI
Synonyms:LACI, TFPI1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000003436.14
HGNCiHGNC:11760 TFPI
MIMi152310 gene
neXtProtiNX_P10646

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi64K → I: Abolishes inhibition of VII(a)/TF. 1
Mutagenesisi135R → L: Abolishes inhibition of X(a). 1
Mutagenesisi227R → L: Abolishes inhibition of VII(a)/TF. 1

Organism-specific databases

DisGeNETi7035
OpenTargetsiENSG00000003436
PharmGKBiPA36475

Chemistry databases

ChEMBLiCHEMBL3713062
DrugBankiDB00036 Coagulation factor VIIa Recombinant Human
DB06779 Dalteparin

Polymorphism and mutation databases

BioMutaiTFPI
DMDMi125932

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 283 PublicationsAdd BLAST28
ChainiPRO_000001687129 – 304Tissue factor pathway inhibitor1 PublicationAdd BLAST276

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi42O-linked (GalNAc...) threonine; partial1 Publication1
Disulfide bondi54 ↔ 104PROSITE-ProRule annotation
Disulfide bondi63 ↔ 87PROSITE-ProRule annotation
Disulfide bondi79 ↔ 100PROSITE-ProRule annotation
Disulfide bondi125 ↔ 175
Disulfide bondi134 ↔ 158
Glycosylationi145N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi150 ↔ 171
Glycosylationi195N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi202O-linked (GalNAc...) serine; partial2 Publications1
Glycosylationi203O-linked (GalNAc...) threonine2 Publications1
Disulfide bondi217 ↔ 267
Disulfide bondi226 ↔ 250
Disulfide bondi242 ↔ 263

Post-translational modificationi

O-glycosylated.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei256Not glycosylated1

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

EPDiP10646
MaxQBiP10646
PaxDbiP10646
PeptideAtlasiP10646
PRIDEiP10646
ProteomicsDBi52636
52637 [P10646-2]

PTM databases

GlyConnecti602
iPTMnetiP10646
PhosphoSitePlusiP10646
UniCarbKBiP10646

Miscellaneous databases

PMAP-CutDBiP10646

Expressioni

Tissue specificityi

Mostly in endothelial cells.

Gene expression databases

BgeeiENSG00000003436 Expressed in 200 organ(s), highest expression level in placenta
CleanExiHS_TFPI
ExpressionAtlasiP10646 baseline and differential
GenevisibleiP10646 HS

Organism-specific databases

HPAiCAB020842
HPA005575

Interactioni

Protein-protein interaction databases

BioGridi112893, 13 interactors
CORUMiP10646
STRINGi9606.ENSP00000233156

Structurei

Secondary structure

1304
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP10646
SMRiP10646
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10646

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 104BPTI/Kunitz inhibitor 1PROSITE-ProRule annotationAdd BLAST51
Domaini125 – 175BPTI/Kunitz inhibitor 2PROSITE-ProRule annotationAdd BLAST51
Domaini217 – 267BPTI/Kunitz inhibitor 3PROSITE-ProRule annotationAdd BLAST51

Domaini

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

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG4295 Eukaryota
ENOG410XQNP LUCA
GeneTreeiENSGT00740000114929
HOGENOMiHOG000231818
HOVERGENiHBG056804
InParanoidiP10646
KOiK03909
OMAiFIQRISK
OrthoDBiEOG091G14M8
PhylomeDBiP10646
TreeFamiTF315349

Family and domain databases

CDDicd00109 KU, 3 hits
Gene3Di4.10.410.10, 3 hits
InterProiView protein in InterPro
IPR002223 Kunitz_BPTI
IPR036880 Kunitz_BPTI_sf
IPR020901 Prtase_inh_Kunz-CS
IPR008296 TFPI-like
IPR029864 TFPI1
PANTHERiPTHR10083:SF317 PTHR10083:SF317, 1 hit
PfamiView protein in Pfam
PF00014 Kunitz_BPTI, 3 hits
PIRSFiPIRSF001620 TFPI, 1 hit
PRINTSiPR00759 BASICPTASE
SMARTiView protein in SMART
SM00131 KU, 3 hits
SUPFAMiSSF57362 SSF57362, 3 hits
PROSITEiView protein in PROSITE
PS00280 BPTI_KUNITZ_1, 3 hits
PS50279 BPTI_KUNITZ_2, 3 hits

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.iShow all

Isoform Alpha (identifier: P10646-1) [UniParc]FASTAAdd to basket
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.

« Hide
        10         20         30         40         50
MIYTMKKVHA LWASVCLLLN LAPAPLNADS EEDEEHTIIT DTELPPLKLM
60 70 80 90 100
HSFCAFKADD GPCKAIMKRF FFNIFTRQCE EFIYGGCEGN QNRFESLEEC
110 120 130 140 150
KKMCTRDNAN RIIKTTLQQE KPDFCFLEED PGICRGYITR YFYNNQTKQC
160 170 180 190 200
ERFKYGGCLG NMNNFETLEE CKNICEDGPN GFQVDNYGTQ LNAVNNSLTP
210 220 230 240 250
QSTKVPSLFE FHGPSWCLTP ADRGLCRANE NRFYYNSVIG KCRPFKYSGC
260 270 280 290 300
GGNENNFTSK QECLRACKKG FIQRISKGGL IKTKRKRKKQ RVKIAYEEIF

VKNM
Length:304
Mass (Da):35,015
Last modified:July 1, 1989 - v1
Checksum:i5281E32B758B44FE
GO
Isoform Beta (identifier: P10646-2) [UniParc]FASTAAdd to basket
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.
Show »
Length:251
Mass (Da):28,653
Checksum:i9B3F276A52B4F0B9
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JKV3C9JKV3_HUMAN
Tissue factor pathway inhibitor
TFPI
215Annotation score:
C9JT76C9JT76_HUMAN
Tissue factor pathway inhibitor
TFPI
105Annotation score:
C9JQ14C9JQ14_HUMAN
Tissue factor pathway inhibitor
TFPI
106Annotation score:
C9J103C9J103_HUMAN
Tissue factor pathway inhibitor
TFPI
76Annotation score:
C9JP39C9JP39_HUMAN
Tissue factor pathway inhibitor
TFPI
61Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012004292V → M1 PublicationCorresponds to variant dbSNP:rs5940Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003030210 – 251EFHGP…YSGCG → VTKEGTNDGWKNAAHIYQVF LNAFCIHASMFFLGLDSISC LC in isoform Beta. 2 PublicationsAdd BLAST42
Alternative sequenceiVSP_003031252 – 304Missing in isoform Beta. 2 PublicationsAdd BLAST53

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03225 mRNA Translation: AAA52022.1
M58650
, M58644, M58645, M58646, M58647, M58648, M58649 Genomic DNA Translation: AAA59480.1
M59499
, 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
CCDSiCCDS2294.1 [P10646-1]
CCDS33349.1 [P10646-2]
PIRiA23712 TIHUGK
RefSeqiNP_001027452.1, NM_001032281.3 [P10646-2]
NP_001305870.1, NM_001318941.2 [P10646-2]
NP_001316168.1, NM_001329239.1 [P10646-1]
NP_001316169.1, NM_001329240.1 [P10646-1]
NP_001316170.1, NM_001329241.1 [P10646-1]
NP_006278.1, NM_006287.5 [P10646-1]
XP_005246876.1, XM_005246819.1 [P10646-1]
XP_006712783.1, XM_006712720.3 [P10646-1]
XP_011510011.1, XM_011511709.2 [P10646-1]
UniGeneiHs.516578

Genome annotation databases

EnsembliENST00000233156; ENSP00000233156; ENSG00000003436 [P10646-1]
ENST00000339091; ENSP00000342306; ENSG00000003436 [P10646-2]
ENST00000392365; ENSP00000376172; ENSG00000003436 [P10646-1]
ENST00000409676; ENSP00000386344; ENSG00000003436 [P10646-2]
GeneIDi7035
KEGGihsa:7035
UCSCiuc002upy.4 human [P10646-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

TFPI entry

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03225 mRNA Translation: AAA52022.1
M58650
, M58644, M58645, M58646, M58647, M58648, M58649 Genomic DNA Translation: AAA59480.1
M59499
, 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
CCDSiCCDS2294.1 [P10646-1]
CCDS33349.1 [P10646-2]
PIRiA23712 TIHUGK
RefSeqiNP_001027452.1, NM_001032281.3 [P10646-2]
NP_001305870.1, NM_001318941.2 [P10646-2]
NP_001316168.1, NM_001329239.1 [P10646-1]
NP_001316169.1, NM_001329240.1 [P10646-1]
NP_001316170.1, NM_001329241.1 [P10646-1]
NP_006278.1, NM_006287.5 [P10646-1]
XP_005246876.1, XM_005246819.1 [P10646-1]
XP_006712783.1, XM_006712720.3 [P10646-1]
XP_011510011.1, XM_011511709.2 [P10646-1]
UniGeneiHs.516578

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ADZNMR-A118-182[»]
1IRHNMR-A210-270[»]
1TFXX-ray2.60C/D121-178[»]
4BQDX-ray2.48A/B29-107[»]
4DTGX-ray1.80K119-178[»]
5NMVX-ray1.65K29-107[»]
ProteinModelPortaliP10646
SMRiP10646
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112893, 13 interactors
CORUMiP10646
STRINGi9606.ENSP00000233156

Chemistry databases

ChEMBLiCHEMBL3713062
DrugBankiDB00036 Coagulation factor VIIa Recombinant Human
DB06779 Dalteparin

Protein family/group databases

MEROPSiI02.950

PTM databases

GlyConnecti602
iPTMnetiP10646
PhosphoSitePlusiP10646
UniCarbKBiP10646

Polymorphism and mutation databases

BioMutaiTFPI
DMDMi125932

Proteomic databases

EPDiP10646
MaxQBiP10646
PaxDbiP10646
PeptideAtlasiP10646
PRIDEiP10646
ProteomicsDBi52636
52637 [P10646-2]

Protocols and materials databases

DNASUi7035
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000233156; ENSP00000233156; ENSG00000003436 [P10646-1]
ENST00000339091; ENSP00000342306; ENSG00000003436 [P10646-2]
ENST00000392365; ENSP00000376172; ENSG00000003436 [P10646-1]
ENST00000409676; ENSP00000386344; ENSG00000003436 [P10646-2]
GeneIDi7035
KEGGihsa:7035
UCSCiuc002upy.4 human [P10646-1]

Organism-specific databases

CTDi7035
DisGeNETi7035
EuPathDBiHostDB:ENSG00000003436.14
GeneCardsiTFPI
HGNCiHGNC:11760 TFPI
HPAiCAB020842
HPA005575
MIMi152310 gene
neXtProtiNX_P10646
OpenTargetsiENSG00000003436
PharmGKBiPA36475
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4295 Eukaryota
ENOG410XQNP LUCA
GeneTreeiENSGT00740000114929
HOGENOMiHOG000231818
HOVERGENiHBG056804
InParanoidiP10646
KOiK03909
OMAiFIQRISK
OrthoDBiEOG091G14M8
PhylomeDBiP10646
TreeFamiTF315349

Enzyme and pathway databases

ReactomeiR-HSA-140834 Extrinsic Pathway of Fibrin Clot Formation
SIGNORiP10646

Miscellaneous databases

ChiTaRSiTFPI human
EvolutionaryTraceiP10646
GeneWikiiTissue_factor_pathway_inhibitor
GenomeRNAii7035
PMAP-CutDBiP10646
PROiPR:P10646
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000003436 Expressed in 200 organ(s), highest expression level in placenta
CleanExiHS_TFPI
ExpressionAtlasiP10646 baseline and differential
GenevisibleiP10646 HS

Family and domain databases

CDDicd00109 KU, 3 hits
Gene3Di4.10.410.10, 3 hits
InterProiView protein in InterPro
IPR002223 Kunitz_BPTI
IPR036880 Kunitz_BPTI_sf
IPR020901 Prtase_inh_Kunz-CS
IPR008296 TFPI-like
IPR029864 TFPI1
PANTHERiPTHR10083:SF317 PTHR10083:SF317, 1 hit
PfamiView protein in Pfam
PF00014 Kunitz_BPTI, 3 hits
PIRSFiPIRSF001620 TFPI, 1 hit
PRINTSiPR00759 BASICPTASE
SMARTiView protein in SMART
SM00131 KU, 3 hits
SUPFAMiSSF57362 SSF57362, 3 hits
PROSITEiView protein in PROSITE
PS00280 BPTI_KUNITZ_1, 3 hits
PS50279 BPTI_KUNITZ_2, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiTFPI1_HUMAN
AccessioniPrimary (citable) accession number: P10646
Secondary accession number(s): O95103, Q53TS4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: September 12, 2018
This is version 217 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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