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FLASH GENE
Symbol TEK contributors: mct/pgu - updated : 09-12-2013
HGNC name TEK tyrosine kinase, endothelial
HGNC id 11724
Corresponding disease
VMCM familial venous malformation, multiple cutaneous and mucosal
Location 9p21.2      Physical location : 27.109.146 - 27.230.171
Synonym name
  • endothelial-specific receptor for angiopoietin-1
  • venous malformations, multiple cutaneous and mucosal
  • CD202b antigen
  • tunica interna endothelial cell kinase
  • soluble TIE2 variant 2
  • angiopoietin-1 receptor
  • Synonym symbol(s) TIE2, CD202B, TIE-2, VMCM1
    EC.number 2.7.10.1
    DNA
    TYPE functioning gene
    STRUCTURE 121.03 kb     23 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • promoter contains closely aligned clusters of three GATA sites and six Ets-binding sites in the first exon
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 1124 12.4 1124 - 1999 10521483
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumearinnercochlea highly
    Lymphoid/Immunelymphatic vessel    
    Nervousbrain   lowly
    Reproductivefemale systemplacenta  highly Homo sapiens
    Respiratoryrespiratory tracttrachea  highly
    Urinarykidneynephronrenal capsuleglomeruluslowly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/lining   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text
  • in chorionic villi tree during early pregnancy
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two immunoglobulin like C2-type domains
  • three epidermal growth factor 3 -like domains
  • three fibronectin-type III homology domains
  • a protein kinase domain
  • HOMOLOGY
    interspecies homolog to rattus Tek (93.74 pc)
    homolog to murine Tek (90.61 pc)
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • CATEGORY enzyme , signaling , receptor membrane tyrosine kinase
    SUBCELLULAR LOCALIZATION     plasma membrane
    text localized with PLD1 in caveolae
    basic FUNCTION
  • required for blood vessel formation and maintenance
  • involved in angiogenesis (in maintenance and/or remodeling of the adult vasculature and regulation during luteinization, luteolysis and rescue)
  • protein-tyrosine kinase receptor that is specifically expressed in endothelial cells
  • has dual roles in promoting angiogenesis and stabilizing blood vessels ligand-independent dimerization of TEK
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • ANGPT1/TEK signaling has a pivotal role in embryonic stem cell- endothelial cell differentiation
  • a component
  • ANGPT1/TEK axis modulates the expression and function of ABC transporters in glioma cells and brain tumor stem cells
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • receptor of ANGPT1
  • HOXA13 directly regulates TEK and FOXF1 in the placental labyrinth endothelia
  • interacting with ABCG2, ABCC2 (downmodulation of ABCG2 or ABCC2 resulted in the inability of TEK activation to induce a chemoresistant phenotype)
  • bind to GATA3
  • TIE1-TEK interactions are dynamic, inhibitory, and differentially modulated by ANGPT1 and ANGPT2
  • ST14 interacts with TEK and degrades the TEK extracellular portion that contains the ligand-binding domain
  • molecular balance between receptor tyrosine kinases TIE1 and TEK is dynamically controlled by VEGF and TNF and regulates angiopoietin signalling
  • expression level of TIE1 and its physical interaction with TEK defines whether ANGPT2 functions as a TEK2 agonist or antagonist, thereby determining the context-dependent differential endothelial sensitivity to ANGPT2
  • ANGPT1 signaling via the TEK receptor regulates vascular and hematopoietic systems
  • ligand-independent dimerization of TEK is essential for a strong response upon stimulation with high dose ANGPT1
  • under hypoxic conditions, TIE1 is critical for reducing ANGPT1-induced TEK activity and angiogenesis
  • overexpression of CASP5 can promote the angiogenesis significantly, possibly by inhibiting the ANGPT1/TEK pathway and promoting VEGFA pathway
  • cell & other
    REGULATION
    activated by by its ligand, angiopoietin ANGPT1
    Other regulated by shear stress
    ASSOCIATED DISORDERS
    corresponding disease(s) VMCM
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    in pulmonary hypertension
    constitutional somatic mutation      
    cause solitary and multiple sporadic venous malformations
    tumoral       gain of function
    may be important in modifying the evolution of gliomas during conventional chemotherapy regimens, and open new avenues for the search of more effective therapies to avoid the inevitable brain tumor recurrence
    constitutional somatic mutation      
    in venous malformations (VM)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousvascular 
    potential therapeutic targets for venous malformations
    ANIMAL & CELL MODELS