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FLASH GENE
Symbol TFPI2 contributors: mct - updated : 23-12-2014
HGNC name tissue factor pathway inhibitor 2
HGNC id 11761
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