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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
    Physical map
    LOC51198 9p21-p22 susceptibility protein NSG-x CDKN2A 9p21.3 cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) CDKN2B 9p21.3 cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) LOC392295 9 similar to ubiquitin A-52 residue ribosomal protein fusion product 1 DMRTA1 9p21.2 DMRT-like family A1 LOC392296 9 similar to Chloride intracellular channel protein 4 (Intracellular chloride ion channel protein p64H1) LOC138267 9p21.2 similar to hypothetical protein ELAVL2 9p21 ELAV (embryonic lethal, abnormal vision, Drosophila)-like 2 (Hu antigen B) LOC389707 9 LOC389707 LOC389708 9 hypothetical gene supported by BC017510; BC046919 FLJ13657 PLAA 9p21 phospholipase A2-activating protein CCDC2 9p21.1 coiled-coil domain containing 2 LRRC19 9 leucine rich repeat containing 19 TEK 9p21 TEK tyrosine kinase, endothelial (venous malformations, multiple cutaneous and mucosal) LOC392297 9 similar to elongin A binding protein 1 C9orf11 9p21 chromosome 9 open reading frame 11 MOB3B IFNK  interferon, kappa C9orf72 9p21.1 chromosome 9 open reading frame 72 LOC392298 9 similar to meningioma-expressed antigen 11 FLJ31810 9p21.1-p13.3 hypothetical protein FLJ31810 LOC286239 9p13.3 similar to NAD-dependent malic enzyme, mitochondrial precursor (NAD-ME) (Malic enzyme 2) LOC389709 9 hypothetical gene supported by AY117688; NM_018158 LOC340493 9p13.3 similar to Heterogeneous nuclear ribonucleoprotein G (hnRNP G) (RNA binding motif protein, X chromosome) (Glycoprotein p43) LOC158200 9p13.3 similar to 40S ribosomal protein S26 LOC392299 9 similar to Ferritin light chain (Ferritin L subunit) LOC138412 9p13.3 similar to ADP,ATP carrier protein, liver isoform T2 (ADP/ATP translocase 3) (Adenine nucleotide translocator 3) (ANT 3) LOC392300 9 similar to High mobility group protein 4-like (HMG-4L)
    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
  • 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