TFPI

Protein identityUniProt · HPA

UniProt accession

P10646

Gene

TFPI

Ensembl

ENSG00000003436

Chromosome

2

Canonical length

304 aa

Protein class

Candidate cardiovascular disease genes, FDA approved drug targets, Plasma proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a Kunitz-type serine protease inhibitor that regulates the tissue factor (TF)-dependent pathway of blood coagulation. The coagulation process initiates with the formation of a factor VIIa-TF complex, which proteolytically activates additional proteases (factors IX and X) and ultimately leads to the formation of a fibrin clot. The product of this gene inhibits the activated factor X and VIIa-TF proteases in an autoregulatory loop. Inhibition of the encoded protein restores hemostasis in animal models of hemophilia. This gene encodes multiple protein isoforms that differ in their inhibitory activity, specificity and cellular localization. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

304 residues, UniProt reviewed canonical sequence.

>P10646|TFPI
     1  MIYTMKKVHA LWASVCLLLN LAPAPLNADS EEDEEHTIIT DTELPPLKLM HSFCAFKADD
    61  GPCKAIMKRF FFNIFTRQCE EFIYGGCEGN QNRFESLEEC KKMCTRDNAN RIIKTTLQQE
   121  KPDFCFLEED PGICRGYITR YFYNNQTKQC ERFKYGGCLG NMNNFETLEE CKNICEDGPN
   181  GFQVDNYGTQ LNAVNNSLTP QSTKVPSLFE FHGPSWCLTP ADRGLCRANE NRFYYNSVIG
   241  KCRPFKYSGC GGNENNFTSK QECLRACKKG FIQRISKGGL IKTKRKRKKQ RVKIAYEEIF
   301  VKNM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TFPI can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.45

Highest tissue expression

254 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TFPI.

Disease | AutoantibodyPubMed

Conditions in which antibodies against TFPI are reported. Each links to that disease's full target list.

• Antiphospholipid Syndrome 3
• Thrombosis 3

ReferencesPubMed · IEDB

Publications for TFPI from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.56

gnomAD pLI

0.25

gnomAD missense Z

1.31

DepMap mean gene effect

0.14

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood coagulation
• cellular response to steroid hormone stimulus
• negative regulation of blood coagulation

Molecular functions

• endopeptidase inhibitor activity
• serine-type endopeptidase inhibitor activity

Cellular components

• caveola
• cell surface
• extracellular region
• extracellular space
• plasma membrane
• side of membrane

Protein domainsUniProt · Pfam · InterPro

• Pancreatic trypsin inhibitor Kunitz domain
• Tissue factor pathway inhibitor-like
• Proteinase inhibitor I2, Kunitz, conserved site
• Pancreatic trypsin inhibitor Kunitz domain superfamily
• Tissue factor pathway inhibitor/Kunitz-type serine protease inhibitor-like
• Kunitz/Bovine pancreatic trypsin inhibitor domain

KeywordsUniProt

• Blood coagulation
• Disulfide bond
• Endoplasmic reticulum
• Glycoprotein
• GPI-anchor
• Hemostasis
• Lipoprotein
• Membrane
• Microsome
• Protease inhibitor
• Repeat
• Secreted
• Serine protease inhibitor
• Signal