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

    Gene ID: 7035, updated on 2-Oct-2018

    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; Vega:OTTHUMG00000132634
    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 current GRCh38.p12 (GCF_000001405.38) 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 Jun 15 11:32:44 2016

    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, OTTHUMP00000205430, ENST00000339091.8, OTTHUMT00000334643
      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, OTTHUMP00000205431, ENST00000409676.5, OTTHUMT00000334644
      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_001329239.1NP_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_001329240.1NP_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_001329241.1NP_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_006287.5NP_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, ENST00000233156.8
      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:216268
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p12 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
      Related
      OTTHUMP00000163472
      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
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