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FLASH GENE
Symbol TEK contributors: mct/pgu - updated : 07-06-2023
HGNC name TEK tyrosine kinase, endothelial
HGNC id 11724
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessel   moderately Homo sapiens
Hearing/Equilibriumearinnercochlea highly
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 Homo sapiens
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
  • a tyrosine 1106 residue in TEK plays a key role to maintain the stemness features of endothelial progenitor cells (EPCs)
  • 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 extracellular
        plasma membrane,junction
        intracellular
    intracellular,cytoplasm
    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
  • is a tyrosine kinase receptor expressed by endothelial cells that induces signal transduction pathways involved in endothelial biology
  • TEK-expressing macrophages (TEMs) play crucial roles in angiogenesis
  • 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
  • TEK is essential for venous specification and maintenance via AKT1 mediated stabilization of NR2F2
  • 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)
    constitutional somatic mutation      
    in blue rubber bleb nevus syndrome (Bean syndrome)
    constitutional     --other  
    disruption of TEK/angiopoietin signaling and procoagulant changes in endothelial cells in severe COVID-19
    constitutional       loss of function
    disruption of the endothelial TEK axis is a sentinel event in septic disseminated intravascular coagulation (DIC)
    constitutional     --over  
    markedly increased prevalence of endothelial tyrosine kinase receptor (TEK/TIE2)+ macrophages in Alveolar capillary dysplasia (ACD) is a rare lung developmental disorder leading to persistent pulmonary arterial hypertension and fatal outcomes in newborns
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousvascular 
    potential therapeutic targets for venous malformations
    immunologyinfectious 
    activation of TEK with the small molecule AKB-9778 reversed the prothrombotic state induced by COVID-19 plasma in primary endothelial cells
    bloodcoagulation 
    targeting TEK may normalize coagulation in inflammatory states while averting the bleeding risks of current DIC therapies
    ANIMAL & CELL MODELS
  • peritoneal macrophages from Tie2 knockout mice can inhibit the expression of autophagy-related factors and inhibit the expression of angiogenic factor of VEGFA by activating AMPK signaling pathway