Format

Send to:

Choose Destination

TFPI tissue factor pathway inhibitor [ Homo sapiens (human) ]

Gene ID: 7035, updated on 17-Jun-2019

Summary

Official Symbol
TFPIprovided by HGNC
Official Full Name
tissue factor pathway inhibitorprovided by HGNC
Primary source
HGNC:HGNC:11760
See related
Ensembl:ENSG00000003436 MIM:152310
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
EPI; TFI; LACI; TFPI1
Summary
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]
Expression
Broad expression in liver (RPKM 42.6), placenta (RPKM 39.9) and 20 other tissues See more
Orthologs

Genomic context

See TFPI in Genome Data Viewer
Location:
2q32.1
Exon count:
13
Annotation release Status Assembly Chr Location
109.20190607 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (187464230..187554505, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (188328957..188419219, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105373786 Neighboring gene RNA, U6 small nuclear 989, pseudogene Neighboring gene calcitonin receptor like receptor Neighboring gene glyceraldehyde-3-phosphate dehydrogenase pseudogene 59 Neighboring gene uncharacterized LOC105373788 Neighboring gene ST13, Hsp70 interacting protein pseudogene 2

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease.
NHGRI GWA Catalog
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of TFPI PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Complement and Coagulation Cascades, organism-specific biosystem (from WikiPathways)
    Complement and Coagulation Cascades, organism-specific biosystemBlood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the for...
  • Complement and coagulation cascades, organism-specific biosystem (from KEGG)
    Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Complement and coagulation cascades, conserved biosystem (from KEGG)
    Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Extrinsic Pathway of Fibrin Clot Formation, organism-specific biosystem (from REACTOME)
    Extrinsic Pathway of Fibrin Clot Formation, organism-specific biosystemFactor VII, the protease that initiates the normal blood clotting cascade, circulates in the blood in both its proenzyme (factor VII) and its activated (factor VIIa) forms. No clotting occurs, howev...
  • Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystem (from REACTOME)
    Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystemThe formation of a fibrin clot at the site of an injury to the wall of a normal blood vessel is an essential part of the process to stop blood loss after vascular injury. The reactions that lead to ...
  • Hemostasis, organism-specific biosystem (from REACTOME)
    Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
  • Integrated Breast Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Breast Cancer Pathway, organism-specific biosystemThis pathway incorporates the most important proteins for Breast Cancer. The Rp score from the Connectivity-Maps (C-Maps) webserver was used to determine the rank of the most important proteins in Br...
  • Syndecan-4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    Syndecan-4-mediated signaling events, organism-specific biosystem
    Syndecan-4-mediated signaling events

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
endopeptidase inhibitor activity TAS
Traceable Author Statement
more info
PubMed 
serine-type endopeptidase inhibitor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Process Evidence Code Pubs
blood coagulation TAS
Traceable Author Statement
more info
PubMed 
blood coagulation, extrinsic pathway TAS
Traceable Author Statement
more info
 
cellular response to interleukin-1 IEA
Inferred from Electronic Annotation
more info
 
cellular response to lipopolysaccharide IEA
Inferred from Electronic Annotation
more info
 
cellular response to steroid hormone stimulus IEP
Inferred from Expression Pattern
more info
PubMed 
negative regulation of blood coagulation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of endopeptidase activity IEA
Inferred from Electronic Annotation
more info
 
response to estradiol IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
anchored component of membrane IEA
Inferred from Electronic Annotation
more info
 
caveola IDA
Inferred from Direct Assay
more info
PubMed 
cell surface HDA PubMed 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
organelle membrane IEA
Inferred from Electronic Annotation
more info
 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
tissue factor pathway inhibitor
Names
anti-convertin
extrinsic pathway inhibitor
tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor)

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_029714.2 RefSeqGene

    Range
    16269..106531
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001032281.3NP_001027452.1  tissue factor pathway inhibitor isoform b precursor

    See identical proteins and their annotated locations for NP_001027452.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame exon in the 3' coding region compared to variant 1. The encoded isoform (b, also known as TFPIbeta) has a shorter and distinct C-terminus, which includes a glycosylphosphatidylinositol (GPI) anchor attachment site, compared to isoform a. Variants 2 and 3 both encode the same isoform (b).
    Source sequence(s)
    AF021834, BC015514, HY175080
    Consensus CDS
    CCDS33349.1
    UniProtKB/Swiss-Prot
    P10646
    Related
    ENSP00000342306.4, ENST00000339091.8
    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:53104
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
  2. NM_001318941.2NP_001305870.1  tissue factor pathway inhibitor isoform b precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and uses an alternate in-frame exon in the 3' coding region compared to variant 1. The encoded isoform (b, also known as TFPIbeta) has a shorter and distinct C-terminus, which includes a glycosylphosphatidylinositol (GPI) anchor attachment site, compared to isoform a. Variants 2 and 3 both encode the same isoform (b).
    Source sequence(s)
    AF021834, BC015514, HY175080
    Consensus CDS
    CCDS33349.1
    UniProtKB/Swiss-Prot
    P10646
    Related
    ENSP00000386344.1, ENST00000409676.5
    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:53104
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
  3. NM_001329239.2NP_001316168.1  tissue factor pathway inhibitor isoform a precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1 but encodes the same isoform (a, also known as TFPIalpha), which is secreted. Variants 1 and 4-6 encode the same isoform (a).
    Source sequence(s)
    AC007319, AC098485, CA418214
    Consensus CDS
    CCDS2294.1
    UniProtKB/Swiss-Prot
    P10646
    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:216268
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
  4. NM_001329240.2NP_001316169.1  tissue factor pathway inhibitor isoform a precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1 but encodes the same isoform (a, also known as TFPIalpha), which is secreted. Variants 1 and 4-6 encode the same isoform (a).
    Source sequence(s)
    AC007319, AC098485, CA418214
    Consensus CDS
    CCDS2294.1
    UniProtKB/Swiss-Prot
    P10646
    Related
    ENSP00000376172.1, ENST00000392365.5
    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:216268
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
  5. NM_001329241.2NP_001316170.1  tissue factor pathway inhibitor isoform a precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) differs in the 5' UTR compared to variant 1 but encodes the same isoform (a, also known as TFPIalpha), which is secreted. Variants 1 and 4-6 encode the same isoform (a).
    Source sequence(s)
    AC007319, AC098485, CA418214
    Consensus CDS
    CCDS2294.1
    UniProtKB/Swiss-Prot
    P10646
    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:216268
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
  6. NM_006287.6NP_006278.1  tissue factor pathway inhibitor isoform a precursor

    See identical proteins and their annotated locations for NP_006278.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (a, also known as TFPIalpha), which is secreted. Variants 1 and 4-6 encode the same isoform (a).
    Source sequence(s)
    AC007319, CA418214, HY175080, J03225
    Consensus CDS
    CCDS2294.1
    UniProtKB/Swiss-Prot
    P10646
    Related
    ENSP00000233156.3, ENST00000233156.9
    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:216268
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

    Range
    187464230..187554505 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024453058.1XP_024308826.1  tissue factor pathway inhibitor isoform X1

    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:216268
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
  2. XM_011511709.3XP_011510011.1  tissue factor pathway inhibitor isoform X1

    See identical proteins and their annotated locations for XP_011510011.1

    UniProtKB/Swiss-Prot
    P10646
    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:216268
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
  3. XM_006712720.4XP_006712783.1  tissue factor pathway inhibitor isoform X1

    See identical proteins and their annotated locations for XP_006712783.1

    UniProtKB/Swiss-Prot
    P10646
    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:216268
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
  4. XM_024453061.1XP_024308829.1  tissue factor pathway inhibitor isoform X2

    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:53104
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
  5. XM_024453059.1XP_024308827.1  tissue factor pathway inhibitor isoform X2

    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:53104
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
  6. XM_024453060.1XP_024308828.1  tissue factor pathway inhibitor isoform X2

    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:53104
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
  7. XM_024453062.1XP_024308830.1  tissue factor pathway inhibitor isoform X2

    Conserved Domains (2) summary
    cd00109
    Location:123175
    KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
    pfam00014
    Location:53104
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
Support Center