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FLASH GENE
Symbol TFPI2 contributors: mct - updated : 23-12-2014
HGNC name tissue factor pathway inhibitor 2
HGNC id 11761
Location 7q21.3      Physical location : 93.515.744 - 93.520.065
Synonym name placental protein 5,lipoprotein associated coagulation inhibitor factor XI (plasmin,trypsin)
Synonym symbol(s) PP5, TFPI-2, REF1
DNA
TYPE functioning gene
STRUCTURE 4.32 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
cytosine-phosphate-guanine/HTF
Binding site   transcription factor
text structure
  • high GC-rich content without canonical TATA and CAAT boxes but three transcription initiation sites
  • promoter exhibiting typical features of a housekeeping gene
  • several putative binding sites for transcription factors were identified (MyoD, LYF1, NF-Y, GATA, oct-1, AP-1, Sp1, NF1, NF-kappa B and egr-1)
  • MAPPING cloned Y linked   status provisional
    RNA
    TRANSCRIPTS type messenger
    text Identification of a human TFPI-2 splice variant that is upregulated in human tumor tissues
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 splicing 1203 26 235 - 2007 17352822
    - splicing 289 - 96 variant upregulated in human tumor tissues 2007 17352822
    variant generated by splicing of:
  • complete exon 2
  • 15 nucleotides of exon 3
  • 6 nucleotides of intron 3
  • 7 nucleotides of exon 4
  • complete exon 5
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   highly
    Digestiveliver   lowly
     stomach   moderately
    Reproductivefemale systemplacenta  predominantly
    Respiratorylung   moderately
    Urinarykidney   moderately
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  moderately
    Epithelialbarrier/lining  lowly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text placenta, maternal serum, heart, pancreas, embryonic tissue, umbilical cord
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three tandem Kunitz-type (58AA motif containing three intrachain disulfide bonds) domains
  • 22 AA signal peptide
  • eighteen cysteines
  • two canomical N-linked glycosylation sites
  • NLS sequence located in its Lys/Arg-rich C-terminal tail comprising residues 191-211
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to rattus Tfpi2 (56.58 pc)
    homolog to murine Tfpi2 (57.48 pc)
    Homologene
    FAMILY serine protease inhibitor family, Kunitz type
    CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,nucleus
    text
  • associated with the extracellular matrix (cuticle and basement membrane)
  • nuclear localization of TFPI2 was also detected in a variety of endothelial cells constitutively expressing TFPI2, and TFPI2 shuttled to the nucleus by the importin system
  • basic FUNCTION
  • inhibiting strongly a wide variety of serine proteinases (trypsin, plasmin, factor XI and MMPs)
  • playing a major role in cell migration and tumor invasion
  • serine proteinase inhibitor that induces caspase-mediated apoptosis when offered to a variety of tumor cells
  • critical for the regulation of extracellular matrix remodeling and atherosclerotic plaque stability
  • Kunitz-type serine protease inhibitor, tumor suppressor gene in several types of cancer, including glioma
  • Kunitz-type serine proteinase inhibitor whose expression is up-regulated by VEGFA in microvascular and umbilical vein endothelial cells (EC)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text blood coagulation
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ADAMTS1
  • the proteolytic inactivation of TFPI2 by PRSS3 might represent a mechanism favoring cancer by increasing angiogenesis and vascular remodeling
  • cell & other
    REGULATION
    induced by thrombin (thrombin induces TFPI2 expression by a mechanism involving ERK1/2 and JNK phosphorylation, leading finally to NFkB activation)
    Other TFPI2 interacting with, cleaved by and extracellular location modified by ADAMTS1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    silencing by methylation in esophageal squamous cell carcinoma
    tumoral     --low  
    by promoter hypermethylation in nasopharyngeal carcinoma
    Susceptibility
    Variant & Polymorphism other Identification of a human TFPI-2 splice variant that is upregulated in human tumor tissues
    Candidate gene
    Marker
  • may be a useful diagnostic marker for the aggressive phenotype of glial tumors
  • detection of TFPI2 methylation in stool DNA may act as a useful adjunct to the noninvasive strategies for screening of colorectal cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveoesophagus
    potentially important therapeutic role for recombinant TFPI2 in the treatment of malignant esophageal carcinomas
    ANIMAL & CELL MODELS