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Protein

Tissue factor pathway inhibitor

Gene

TFPI

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Keywords - Biological processi

Blood coagulation, Hemostasis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000003436-MONOMER.
ReactomeiR-HSA-140834. Extrinsic Pathway of Fibrin Clot Formation.
SIGNORiP10646.

Protein family/group databases

MEROPSiI02.011.

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

HGNCiHGNC:11760. TFPI.

Subcellular locationi

Isoform Beta :

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB-KW
  • cell surface Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB-KW
  • extracellular region Source: Reactome
  • extracellular space Source: BHF-UCL
  • organelle membrane Source: UniProtKB-SubCell
  • plasma membrane Source: Reactome
Complete GO annotation...

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

DrugBankiDB00036. Coagulation factor VIIa.
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...); 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...)3 Publications1
Disulfide bondi150 ↔ 171
Glycosylationi195N-linked (GlcNAc...)2 Publications1
Glycosylationi202O-linked (GalNAc...); partial2 Publications1
Glycosylationi203O-linked (GalNAc...)2 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.

PTM databases

iPTMnetiP10646.
PhosphoSitePlusiP10646.
UniCarbKBiP10646.

Miscellaneous databases

PMAP-CutDBP10646.

Expressioni

Tissue specificityi

Mostly in endothelial cells.

Gene expression databases

BgeeiENSG00000003436.
CleanExiHS_TFPI.
ExpressionAtlasiP10646. baseline and differential.
GenevisibleiP10646. HS.

Organism-specific databases

HPAiCAB020842.
HPA005575.

Interactioni

Protein-protein interaction databases

BioGridi112893. 13 interactors.
STRINGi9606.ENSP00000233156.

Structurei

Secondary structure

1304
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi31 – 39Combined sources9
Helixi52 – 55Combined sources4
Beta strandi67 – 73Combined sources7
Turni74 – 77Combined sources4
Beta strandi78 – 84Combined sources7
Beta strandi94 – 96Combined sources3
Helixi97 – 104Combined sources8
Beta strandi118 – 120Combined sources3
Helixi123 – 126Combined sources4
Beta strandi138 – 144Combined sources7
Turni145 – 148Combined sources4
Beta strandi149 – 155Combined sources7
Beta strandi157 – 159Combined sources3
Beta strandi165 – 167Combined sources3
Helixi168 – 175Combined sources8
Beta strandi178 – 180Combined sources3
Beta strandi215 – 219Combined sources5
Beta strandi224 – 226Combined sources3
Beta strandi232 – 235Combined sources4
Turni237 – 239Combined sources3
Beta strandi241 – 245Combined sources5
Beta strandi257 – 260Combined sources4
Helixi261 – 267Combined sources7

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[»]
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.

Sequence similaritiesi

Contains 3 BPTI/Kunitz inhibitor domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

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

Family and domain databases

Gene3Di4.10.410.10. 3 hits.
InterProiIPR002223. Kunitz_BPTI.
IPR020901. Prtase_inh_Kunz-CS.
IPR029864. TFPI1.
[Graphical view]
PANTHERiPTHR10083:SF238. PTHR10083:SF238. 1 hit.
PfamiPF00014. Kunitz_BPTI. 3 hits.
[Graphical view]
PRINTSiPR00759. BASICPTASE.
SMARTiSM00131. KU. 3 hits.
[Graphical view]
SUPFAMiSSF57362. SSF57362. 3 hits.
PROSITEiPS00280. BPTI_KUNITZ_1. 3 hits.
PS50279. BPTI_KUNITZ_2. 3 hits.
[Graphical view]

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

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012004292V → M.1 PublicationCorresponds to variant rs5940dbSNPEnsembl.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

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[»]
ProteinModelPortaliP10646.
SMRiP10646.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112893. 13 interactors.
STRINGi9606.ENSP00000233156.

Chemistry databases

DrugBankiDB00036. Coagulation factor VIIa.
DB06779. Dalteparin.

Protein family/group databases

MEROPSiI02.011.

PTM databases

iPTMnetiP10646.
PhosphoSitePlusiP10646.
UniCarbKBiP10646.

Polymorphism and mutation databases

BioMutaiTFPI.
DMDMi125932.

Proteomic databases

EPDiP10646.
MaxQBiP10646.
PaxDbiP10646.
PeptideAtlasiP10646.
PRIDEiP10646.

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.
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

BioCyciZFISH:ENSG00000003436-MONOMER.
ReactomeiR-HSA-140834. Extrinsic Pathway of Fibrin Clot Formation.
SIGNORiP10646.

Miscellaneous databases

ChiTaRSiTFPI. human.
EvolutionaryTraceiP10646.
GeneWikiiTissue_factor_pathway_inhibitor.
GenomeRNAii7035.
PMAP-CutDBP10646.
PROiP10646.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000003436.
CleanExiHS_TFPI.
ExpressionAtlasiP10646. baseline and differential.
GenevisibleiP10646. HS.

Family and domain databases

Gene3Di4.10.410.10. 3 hits.
InterProiIPR002223. Kunitz_BPTI.
IPR020901. Prtase_inh_Kunz-CS.
IPR029864. TFPI1.
[Graphical view]
PANTHERiPTHR10083:SF238. PTHR10083:SF238. 1 hit.
PfamiPF00014. Kunitz_BPTI. 3 hits.
[Graphical view]
PRINTSiPR00759. BASICPTASE.
SMARTiSM00131. KU. 3 hits.
[Graphical view]
SUPFAMiSSF57362. SSF57362. 3 hits.
PROSITEiPS00280. BPTI_KUNITZ_1. 3 hits.
PS50279. BPTI_KUNITZ_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTFPI1_HUMAN
AccessioniPrimary (citable) accession number: P10646
Secondary accession number(s): O95103, Q53TS4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 30, 2016
This is version 204 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.