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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
    Physical map
    MTERF 7q21-q22 ankyrin repeat and SOCS box-containing 4 AKAP9 7q21-q22 a kinase (PRKA) anchor protein (yotiao) 9 CYP51A1 7q21.2-q21.3 cytochrome P450, family 51, subfamily A, polypeptide 1 LOC389532 7 similar to hypothetical protein 4932412H11 CCM1 7q21-q22 cerebral cavernous malformations 1 LOC392070 7 similar to RIKEN cDNA 4930500J03 LOC392071 7 similar to RIKEN cDNA 2810014D17 ODAG 7q21-q22 ocular development-associated gene PEX1 7q21-q22 peroxisome biogenesis factor 1 DKFZP564O0523 7q21.3 hypothetical protein DKFZp564O0523 MGC16142 7q21.3 hypothetical protein MGC16142 LOC392072 7 similar to hypothetical protein FLJ11767 MGC40405 7q21.3 hypothetical protein MGC40405 CDK6 7q21-q22 cyclin-dependent kinase 6 FLJ20073 7q21.3 FLJ20073 protein FLJ39885 7q21.3 hypothetical protein FLJ39885 LOC253012 7q21.3 hypothetical protein LOC253012 FLJ20097 7q21.3 hypothetical protein FLJ20097 CALCR 7q21.3 calcitonin receptor LOC346588 7q21.3 similar to Protein C6orf66 (HSPC125) (My013 protein) TFPI2 7q22 tissue factor pathway inhibitor 2 GNGT1 7q21.3 guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 1 GNG11 7q21.3 guanine nucleotide binding protein (G protein), gamma 11 BET1 7q21.1-q22 BET1 homolog (S. cerevisiae) COL1A2 7q21.3 collagen, type I, alpha 2 CAS1 7q21.3 O-acetyltransferase SGCE 7q21.3 sarcoglycan, epsilon PEG10 7q21 paternally expressed 10 LOC392073 7 similar to ribosomal protein S3a; 40S ribosomal protein S3a; v-fos transformation effector protein 1 LOC392074 7 similar to dJ133P16.1 (ADP-ribosylation factor 1) PPP1R9A 7q21 protein phosphatase 1, regulatory (inhibitor) subunit 9A PON1 7q21.3 paraoxonase 1 PON3 7q21.3 paraoxonase 3 PON2 7q21.3 paraoxonase 2 ASB4 7q21-q22 ankyrin repeat and SOCS box-containing 4 PDK4 7q21.3 pyruvate dehydrogenase kinase, isoenzyme 4 LOC389533 7 LOC389533 DNCI1 7q21.3 dynein, cytoplasmic, intermediate polypeptide 1
    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