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TEK Gene

protein-coding   GIFtS: 74
GCID: GC09P027109

TEK Tyrosine Kinase, Endothelial

(Previous names: venous malformations, multiple cutaneous and mucosal)
(Previous symbol: VMCM)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
TEK Tyrosine Kinase, Endothelial1 2     EC 2.7.10.13 8
VMCM1 2 3 5     Venous Malformations, Multiple Cutaneous And Mucosal1
TIE22 3 5     CD202B2
Endothelial Tyrosine Kinase2 3     TIE-22
Tunica Interna Endothelial Cell Kinase2 3     Angiopoietin-1 Receptor2
Tyrosine Kinase With Ig And EGF Homology Domains-22 3     CD202b Antigen3
Tyrosine-Protein Kinase Receptor TEK2 3     hTIE23
Tyrosine-Protein Kinase Receptor TIE-22 3     P140 TEK3
VMCM12 3     EC 2.7.108

External Ids:    HGNC: 117241   Entrez Gene: 70102   Ensembl: ENSG000001201567   OMIM: 6002215   UniProtKB: Q027633   

Export aliases for TEK gene to outside databases

Previous GC identifers: GC09P027421 GC09P027278 GC09P027099


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TEK Gene:
This gene encodes a receptor that belongs to the protein tyrosine kinase Tie2 family. The encoded protein
possesses a unique extracellular region that contains two immunoglobulin-like domains, three epidermal growth
factor (EGF)-like domains and three fibronectin type III repeats. The ligand angiopoietin-1 binds to this
receptor and mediates a signaling pathway that functions in embryonic vascular development. Mutations in this
gene are associated with inherited venous malformations of the skin and mucous membranes. Alternative splicing
results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have
been described, but their full-length nature is not known. (provided by RefSeq, Feb 2014)

GeneCards Summary for TEK Gene:
TEK (TEK tyrosine kinase, endothelial) is a protein-coding gene. Diseases associated with TEK include multiple cutaneous and mucosal venous malformations, and intramuscular hemangioma. GO annotations related to this gene include protein tyrosine kinase activity and receptor activity. An important paralog of this gene is TIE1.

UniProtKB/Swiss-Prot: TIE2_HUMAN, Q02763
Function: Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates
angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of
the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing
the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. Required for normal
angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth,
activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular
stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1
oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this
leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating
endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix,
leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases
MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers
receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for
scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote
TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the
same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic
processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates
signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1
and TIE1

Gene Wiki entry for TEK (TEK tyrosine kinase) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000009.12  NT_008413.19  NC_018920.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the TEK gene promoter:
         AhR   RP58   NF-1   AML1a   GATA-3   CUTL1   GATA-1   GATA-2   FOXJ2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidTEK promoter sequence
   Search Chromatin IP Primers for TEK

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TEK


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 9p21   Ensembl cytogenetic band:  9p21.2   HGNC cytogenetic band: 9p21

TEK Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TEK gene location

GeneLoc information about chromosome 9         GeneLoc Exon Structure

GeneLoc location for GC09P027109:  view genomic region     (about GC identifiers)

Start:
27,109,139 bp from pter      End:
27,230,173 bp from pter
Size:
121,035 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: TIE2_HUMAN, Q02763 (See protein sequence)
Recommended Name: Angiopoietin-1 receptor precursor  
Size: 1124 amino acids; 125830 Da
Subunit: Homodimer. Heterodimer with TIE1. Interacts with ANGPT1, ANGPT2 and ANGPT4. At cell-cell contacts in
quiescent cells, forms a signaling complex composed of ANGPT1 plus TEK molecules from two adjoining cells. In the
absence of endothelial cell-cell contacts, interaction with ANGPT1 mediates contacts with the extracellular
matrix. Interacts with PTPRB; this promotes endothelial cell-cell adhesion. Interacts with DOK2, GRB2, GRB7,
GRB14, PIK3R1 and PTPN11/SHP2. Colocalizes with DOK2 at contacts with the extracellular matrix in migrating
cells. Interacts (tyrosine phosphorylated) with TNIP2. Interacts (tyrosine phosphorylated) with SHC1 (via SH2
domain)
Selected PDB 3D structures from and Proteopedia for TEK (see all 10):
1FVR (3D)        2GY5 (3D)        2GY7 (3D)        2OO8 (3D)        2OSC (3D)        2P4I (3D)    
Secondary accessions: A8K6W0 B4DH20 B4DHD3 D3DRK5 E7EWI2 Q5TCU2 Q8IV34
Alternative splicing: 3 isoforms:  Q02763-1   Q02763-2   Q02763-3   

Explore the universe of human proteins at neXtProt for TEK: NX_Q02763

Explore proteomics data for TEK at MOPED

Post-translational modifications: 

  • Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2)1
  • Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e.
    one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation
    occurs in a sequential manner, where Tyr-992 in the kinase activation loop is phosphorylated first, followed by
    autophosphorylation at Tyr-1108 and at additional tyrosine residues. ANGPT1-induced phosphorylation is impaired
    during hypoxia, due to increased expression of ANGPT2. Phosphorylation is important for interaction with GRB14,
    PIK3R1 and PTPN11. Phosphorylation at Tyr-1102 is important for interaction with SHC1, GRB2 and GRB7.
    Phosphorylation at Tyr-1108 is important for interaction with DOK2 and for coupling to downstream signal
    transduction pathways in endothelial cells. Dephosphorylated by PTPRB1
  • Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation1
  • Glycosylation2 at Asn140, Asn158, Asn399, Asn438, Asn464, Asn560, Asn596, Asn649, Asn691
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for TEK (Q02763) (see all 13)
     NCDDEVY  FTYAGID  RDLAARN  QCWREKP 


    See TEK Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_000450.2  NP_001277006.1  NP_001277007.1  

    ENSEMBL proteins: 
     ENSP00000430686   ENSP00000369375   ENSP00000383977   ENSP00000428337  
    Reactome Protein details: Q02763

    TEK Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant TEK Protein
    R&D Systems Recombinant & Natural Proteins for TEK (Tie-2)
    Enzo Life Sciences proteins for TEK
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for TEK
    OriGene Custom MassSpec
    OriGene Custom Protein Services for TEK
    GenScript Custom Purified and Recombinant Proteins Services for TEK
    Novus Biologicals TEK Proteins
    Novus Biologicals TEK Lysate
    Sino Biological Recombinant Protein for TEK
    Sino Biological Cell Lysate for TEK
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

    TEK Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of TEK
    R&D Systems Antibodies for TEK (Tie-2)
    Cell Signaling Technology (CST) Antibodies for TEK  (TIE2)
    OriGene Antibodies for TEK
    OriGene Custom Antibody Services for TEK
    Novus Biologicals TEK Antibodies
    Abcam antibodies for TEK
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibody for TEK
    LSBio Antibodies in human, mouse, rat for TEK

    TEK Assay Products:

    EMD Millipore Kits and Assays for the Analysis of TEK
    OriGene Custom Assay Services for TEK
    R&D Systems ELISAs for TEK (Tie-2)         (see all)
    GenScript TEK-Activity-based Kinase Assay for Compound Screening
    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    FN3: Fibronectin type III domain containing
    CD: CD molecules
    IGD: Immunoglobulin superfamily / Immunoglobulin-like domain containing

    IUPHAR Guide to PHARMACOLOGY protein family classification: TEK tyrosine kinase, endothelial
    Tie family
    TIE family of angiopoietin receptors

    Selected InterPro protein domains (see all 12):
     IPR007110 Ig-like_dom
     IPR017441 Protein_kinase_ATP_BS
     IPR018941 Tyr_kin_Tie2_Ig-like_dom-1_N
     IPR000742 EG-like_dom
     IPR003961 Fibronectin_type3

    Graphical View of Domain Structure for InterPro Entry Q02763

    ProtoNet protein and cluster: Q02763

    2 Blocks protein domains:
    IPB006210 Type I EGF
    IPB008266 Tyrosine protein kinase


    UniProtKB/Swiss-Prot: TIE2_HUMAN, Q02763
    Domain: The soluble extracellular domain is functionally active in angiopoietin binding and can modulate the
    activity of the membrane-bound form by competing for angiopoietins
    Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. Tie subfamily
    Similarity: Contains 3 EGF-like domains
    Similarity: Contains 3 fibronectin type-III domains
    Similarity: Contains 2 Ig-like C2-type (immunoglobulin-like) domains
    Similarity: Contains 1 protein kinase domain


    TEK for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TIE2_HUMAN, Q02763
    Function: Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates
    angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of
    the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing
    the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. Required for normal
    angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth,
    activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular
    stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1
    oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this
    leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating
    endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix,
    leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases
    MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers
    receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for
    scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote
    TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the
    same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic
    processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates
    signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1
    and TIE1
    Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
    Enzyme regulation: Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at
    Tyr-992 on the kinase activation loop. Inhibited by staurosporine, K252a, PP2, damnacanthal, SB203580, CEP-11207,
    CEP-11981 and CE-245677. Inhibited by triazine, thienopyrimidine and thiazolopyrimidine derivatives

         Genatlas biochemistry entry for TEK:
    endothelial cell specific receptor tyrosine kinase,with extracellular immunoglobulin,epidermal growth
    factor,fibronectin-type III homology domains,involved in angiogenesis (in maintenance and/or remodeling of the
    adult vasculature)

         Enzyme Numbers (IUBMB): EC 2.7.10.11 2 EC 2.7.102

         Gene Ontology (GO): Selected molecular function terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity TAS8382358
    GO:0004713protein tyrosine kinase activity TAS--
    GO:0004714transmembrane receptor protein tyrosine kinase activity IEA--
    GO:0004872receptor activity TAS10766762
    GO:0005515protein binding IPI19167335
         
    TEK for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for TEK:
     Decreased substrate adherent c  Increased mitotic index 

         10 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Tek):
     cardiovascular system  cellular  embryogenesis  growth/size/body  hematopoietic system 
     homeostasis/metabolism  mortality/aging  muscle  nervous system  normal 

    TEK for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for TEK: Tektm1Sato Tektm1Dmt

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TEK
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for TEK

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for TEK
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for TEK

    miRNA
    Products:
        
    miRTarBase miRNAs that target TEK:
    hsa-mir-126-3p (MIRT006883)

    Block miRNA regulation of human, mouse, rat TEK using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TEK (see all 14):
    hsa-miR-448 hsa-miR-148b hsa-miR-586 hsa-miR-548o hsa-miR-1179 hsa-miR-152 hsa-miR-144 hsa-miR-656
    SwitchGear 3'UTR luciferase reporter plasmidTEK 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for TEK
    Predesigned siRNA for gene silencing in human, mouse, rat TEK

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for TEK

    Clone
    Products:
         
    OriGene clones in human, mouse for TEK (see all 10)
    OriGene ORF clones in mouse, rat for TEK
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: TEK (NM_000459)
    Sino Biological Human cDNA Clone for TEK
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TEK
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TEK

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for TEK
    Browse ESI BIO Cell Lines and PureStem Progenitors for TEK 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TEK


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    TIE2_HUMAN, Q02763: Cell membrane; Single-pass type I membrane protein. Cell junction. Cell junction, focal
    adhesion. Cytoplasm, cytoskeleton. Secreted. Note=Recruited to cell-cell contacts in quiescent endothelial cells.
    Colocalizes with the actin cytoskeleton and at actin stress fibers during cell spreading. Recruited to the lower
    surface of migrating cells, especially the rear end of the cell. Proteolytic processing gives rise to a soluble
    extracellular domain that is secreted
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    extracellular5
    plasma membrane5
    endoplasmic reticulum2
    nucleus1
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001725colocalizes with stress fiber IDA18425119
    GO:0005576extracellular region IEA--
    GO:0005737cytoplasm IEA--
    GO:0005884colocalizes with actin filament IDA18425119
    GO:0005886plasma membrane TAS--

    TEK for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for TEK About   (see all 22)  
    See pathways by source

    SuperPathContained pathways About
    1Immune response IL 23 signaling pathway
    Development Angiopoietin Tie2 signaling0.38
    Angiopoietin receptor Tie2-mediated signaling0.32
    Angiopoietin-TIE2 Signaling0.36
    2GPCR Pathway
    Ras Pathway0.73
    Breast Cancer Regulation by Stathmin10.58
    Paxillin Interactions0.73
    NFAT in Immune Response0.58
    GPCR Pathway0.62
    Estrogen Pathway0.55
    Pancreatic Adenocarcinoma0.59
    P2Y Receptor Signaling0.38
    3ERK Signaling
    Rho Family GTPases0.61
    Molecular Mechanisms of Cancer0.51
    ERK Signaling0.61
    ILK Signaling0.49
    MAPK Signaling0.58
    4Nanog in Mammalian ESC Pluripotency
    Nanog in Mammalian ESC Pluripotency0.61
    14-3-3 Induced Intracellular Signaling0.59
    GSK3 Signaling0.61
    eNOS Signaling0.48
    5Akt Signaling
    Akt Signaling0.60
    Tec Kinases Signaling0.55
    p38 Signaling0.60

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for TEK
        Akt Signaling Pathway

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for TEK (see all 32)
        Paxillin Interactions
    Molecular Mechanisms of Cancer
    Antioxidant Action of Vitamin-C
    Intracellular Calcium Signaling
    JNK Pathway

    2 Cell Signaling Technology (CST) Pathways for TEK
        Angiogenesis
    Tyrosine Kinases / Adaptors

    2 GeneGo (Thomson Reuters) Pathways for TEK
        G-protein signaling H-RAS regulation pathway
    Development Angiopoietin - Tie2 signaling

    2 BioSystems Pathways for TEK
        Angiogenesis
    Angiopoietin receptor Tie2-mediated signaling


    1 Reactome Pathway for TEK
        Tie2 Signaling


    5 Kegg Pathways  (Kegg details for TEK):
        Ras signaling pathway
    Rap1 signaling pathway
    HIF-1 signaling pathway
    PI3K-Akt signaling pathway
    Rheumatoid arthritis


    TEK for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TEK: 
              Cell Surface Markers in human mouse rat
              Endothelial Cell Biology in human mouse rat
              Cancer PathwayFinder in human mouse rat
              Angiogenesis in human mouse rat
              Hematopoiesis in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for TEK

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for TEK (Q027631, 2, 3 ENSP000003839774) via UniProtKB, MINT, STRING, and/or I2D (see all 54)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    SHC1P293532, 3, ENSP000004013034MINT-8026417 MINT-8026432 I2D: score=3 STRING: ENSP00000401303
    ANGPT2O151231, 3, ENSP000003148974EBI-2257090,EBI-2912111 I2D: score=4 STRING: ENSP00000314897
    PTPRBP234671, 3, ENSP000003349284EBI-2257090,EBI-1265766 I2D: score=2 STRING: ENSP00000334928
    PTPN12Q052091, 3, ENSP000002485944EBI-2257090,EBI-2266035 I2D: score=1 STRING: ENSP00000248594
    PTPRKQ152621, 3, ENSP000003572094EBI-2257090,EBI-474052 I2D: score=1 STRING: ENSP00000357209
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 50):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001525angiogenesis ISS--
    GO:0001666response to hypoxia IEA--
    GO:0001934positive regulation of protein phosphorylation IMP18425120
    GO:0001935endothelial cell proliferation ISS--
    GO:0001938positive regulation of endothelial cell proliferation TAS18425120

    TEK for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Enzo Life Sciences drugs & compounds for TEK
      Browse compounds at ApexBio 

    Browse Tocris compounds for TEK (TIE2)

    2 HMDB Compounds for TEK    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    4 DrugBank Compounds for TEK    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    N-{4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDE-- --target--10592235
    Ponatinib -- 943319-70-8targetinhibitor--
    Regorafenib-- 755037-03-7targetinhibitor--
    Vandetanib4-quinazolinamine, N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]- (see all 4)443913-73-3targetinhibitor--

    2 IUPHAR Ligands for TEK (TEK tyrosine kinase, endothelial)    About this table
    LigandTypeActionAffinityPubmed IDs
    angiopoietin-4
    NoneNone--
    angiopoietin-1
    NoneNone--

    Selected Novoseek inferred chemical compound relationships for TEK gene (see all 16)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    vegf 84.1 272 19376222 (7), 15548809 (7), 16891056 (6), 10397264 (5) (see all 99)
    tyrosine 75.7 132 19376222 (4), 10913057 (2), 12609966 (2), 19116766 (2) (see all 99)
    matrigel 51.7 6 19940250 (1), 15501241 (1), 19285068 (1), 12588764 (1)
    tween 33.5 2 16363251 (1), 16164572 (1)
    phosphatidylinositol 18.9 4 19223473 (1), 11002428 (1), 15370298 (1), 10625301 (1)
    nitric oxide 17.4 13 15985432 (2), 17913848 (1), 12388336 (1), 12477527 (1) (see all 10)
    paraffin 10.4 1 17383647 (1)
    ribonucleic acid 3.95 3 11397875 (1), 11095472 (1), 11297624 (1)
    thymidine 0 2 11166279 (1), 10729313 (1)
    oxygen 0 2 10969034 (1)



    TEK for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
    About This Section

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    REFSEQ mRNAs for TEK gene (3 alternative transcripts): 
    NM_000459.4  NM_001290077.1  NM_001290078.1  

    Unigene Cluster for TEK:

    TEK tyrosine kinase, endothelial
    Hs.89640  [show with all ESTs]
    Unigene Representative Sequence: NM_000459
    4 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000519097(uc010mjc.1) ENST00000380036(uc011lnn.1 uc003zqi.4 uc011lno.2 uc011lnp.2)
    ENST00000406359(uc003zqj.1) ENST00000519080
    miRNA
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    hsa-miR-448 hsa-miR-148b hsa-miR-586 hsa-miR-548o hsa-miR-1179 hsa-miR-152 hsa-miR-144 hsa-miR-656
    SwitchGear 3'UTR luciferase reporter plasmidTEK 3' UTR sequence
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      QuantiFast Probe-based Assays in human, mouse, rat TEK

    Additional mRNA sequence: 

    AB086825.1 AB208796.1 AK291775.1 AK294887.1 AK295043.1 AK308447.1 BC035514.1 EU826591.1 
    EU826592.1 L06139.1 

    5 DOTS entries:

    DT.95265085  DT.100671898  DT.75193539  DT.121206559  DT.97786338 

    Selected AceView cDNA sequences (see all 37):

    BP337931 AL698883 H44411 H25908 CA392256 AW020953 BI834412 BX101889 
    BM974183 BP376136 BC035514 AW237436 AB086825 L06139 BU753127 BM972245 
    NM_000459 BM996087 AW103258 AL047086 BP364394 BP344392 BX504714 AW299451 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for TEK    About this scheme

    ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23
    SP1:                                                                                                                                                            
    SP2:                                            -                                                                                                               
    SP3:                                                                                                                                                            


    ECgene alternative splicing isoforms for TEK

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    TEK expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AGTGAATAAA
    TEK Expression
    About this image


    TEK expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 13) fully expand
     
     Endothelium (Cardiovascular System)    fully expand to see all 13 entries
             Angioblasts Embryonic Capillary Plexus
             Human umbilical vein endothelial cells (HUVEC)
             Vascular endothelial growth factor-induced endothelial cells
     
     Heart (Cardiovascular System)    fully expand to see all 5 entries
             Endocardial Cells Endocardium
     
     Lateral Plate Mesoderm (Gastrulation Derivatives)    fully expand to see all 3 entries
             Angioblasts Embryonic Capillary Plexus
     
     Blood (Cardiovascular System)    fully expand to see all 4 entries
             Hematopoietic Stem Cells Hematopoietic Bone Marrow
             Angiogenic cell precursor
     
     Neural Tube (Nervous System)
             Angioblasts Perineural capillary Plexus
    TEK Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TEK Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.89640

    UniProtKB/Swiss-Prot: TIE2_HUMAN, Q02763
    Tissue specificity: Detected in umbilical vein endothelial cells. Proteolytic processing gives rise to a soluble
    extracellular domain that is detected in blood plasma (at protein level). Predominantly expressed in endothelial
    cells and their progenitors, the angioblasts. Has been directly found in placenta and lung, with a lower level in
    umbilical vein endothelial cells, brain and kidney

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TEK: 
              Cell Surface Markers in human mouse rat
              Endothelial Cell Biology in human mouse rat
              Cancer PathwayFinder in human mouse rat
              Angiogenesis in human mouse rat
              Hematopoiesis in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for TEK gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Tek1 , 5 endothelial-specific receptor tyrosine kinase1, 5 88.95(n)1
    93.14(a)1
      4 (43.34 cM)5
    216871  NM_013690.21  NP_038718.21 
     947392895 
    chicken
    (Gallus gallus)
    Aves TEK1 TEK tyrosine kinase, endothelial 71.62(n)
    74(a)
      427368  XM_004949580.1  XP_004949637.1 
    lizard
    (Anolis carolinensis)
    Reptilia TEK6
    TEK tyrosine kinase, endothelial
    69(a)
    1 ↔ 1
    2(58847441-58894847)
    African clawed frog
    (Xenopus laevis)
    Amphibia LOC3982632 angiopoietin receptor Xtie-2 73.44(n)    AY037939.1 
    zebrafish
    (Danio rerio)
    Actinopterygii tie22 endothelium-specific receptor tyrosine kinase 2 74.59(n)   30747  AF053632.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Tie6
    Tie-like receptor tyrosine kinase
    17(a)
    1 → many
    3L(4510698-4532145)
    worm
    (Caenorhabditis elegans)
    Secernentea R151.43 Tyrosine kinase 38(a)
    (best of 7)
      III(7291720-7292812)   --


    ENSEMBL Gene Tree for TEK (if available)
    TreeFam Gene Tree for TEK (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TEK gene
    TIE12  STYK12  
    15 SIMAP similar genes for TEK using alignment to 6 protein entries:     TIE2_HUMAN (see all proteins):
    Tie-2    TIE1    ABL1    SRC    EPHA2    tec
    urf-ret    FGR    CSK    TIE    RYK    FGFR3
    DKFZp434L0319    KIT    TYRO3

    TEK for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for TEK (see all 3488)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 9 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0666064
    Dominantly inherited venous malformations (VMCM)4--see VAR_0666062 Y C mis40--------
    VAR_0418614
    An ovarian serous carcinoma sample4--see VAR_0418612 P A mis40--------
    VAR_0666094
    Dominantly inherited venous malformations (VMCM)4--see VAR_0666092 V L mis40--------
    VAR_0666084
    Dominantly inherited venous malformations (VMCM)4--see VAR_0666082 R C mis40--------
    VAR_0666114
    Dominantly inherited venous malformations (VMCM)4--see VAR_0666112 K N mis40--------
    VAR_0418624
    A renal clear cell carcinoma sample4--see VAR_0418622 A V mis40--------
    VAR_0666074
    Dominantly inherited venous malformations (VMCM)4--see VAR_0666072 R H mis40--------
    VAR_0087164
    Dominantly inherited venous malformations (VMCM)4--see VAR_0087162 Y S mis40--------
    VAR_0666104
    Dominantly inherited venous malformations (VMCM)4--see VAR_0666102 A S mis40--------
    VAR_0357144
    Breast cancer samples4--see VAR_0357142 K N mis40--------

    HapMap Linkage Disequilibrium report for TEK (27109139 - 27230173 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for TEK (see all 11):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv1009235CNV Deletion20482838
    nsv6512CNV Loss18451855
    nsv824895CNV Loss20364138
    nsv892865CNV Gain21882294
    nsv517269CNV Gain19592680
    nsv892862CNV Gain21882294
    nsv471294CNV Gain18288195
    nsv892863CNV Gain21882294
    nsv466336CNV Gain19166990
    esv23509CNV Gain19812545

    Human Gene Mutation Database (HGMD): TEK
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing TEK
    DNA2.0 Custom Variant and Variant Library Synthesis for TEK

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 600221   
    OMIM disorders: 600195  
    UniProtKB/Swiss-Prot: TIE2_HUMAN, Q02763
  • Dominantly inherited venous malformations (VMCM) [MIM:600195]: An error of vascular morphogenesis
    characterized by dilated, serpiginous channels. Note=The disease is caused by mutations affecting the gene
    represented in this entry
  • Note=May play a role in a range of diseases with a vascular component, including neovascularization of
    tumors, psoriasis and inflammation

  • Selected diseases for TEK (see all 99):    
    About MalaCards
    multiple cutaneous and mucosal venous malformations    intramuscular hemangioma    tufted angioma    glomangioma
    endotheliitis    capillary hemangioma    pyogenic granuloma    glomuvenous malformation
    placenta accreta    arteriovenous malformation    polycystic liver disease    hemangioma
    cavernous hemangioma    corneal neovascularization    angioimmunoblastic t-cell lymphoma    critical limb ischemia
    piebaldism    klippel-trenaunay syndrome    solitary fibrous tumor    intermittent claudication


    TEK for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for TEK gene (see all 65)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    neovascularization 74.6 21 13130465 (2), 11915032 (1), 18205179 (1), 16447257 (1) (see all 17)
    malformation venous 71.5 13 9926914 (2), 19079259 (2), 16756945 (2), 11932989 (1) (see all 9)
    tumors 48.7 144 15928093 (6), 11169947 (5), 11309342 (4), 17478063 (4) (see all 66)
    inflammatory breast cancer 48.1 2 15585631 (2)
    corneal neovascularization 35.6 1 10202935 (1)
    granuloma pyogenic 34.3 2 10929871 (2)
    metastasis 28.2 13 19487284 (2), 12527939 (2), 15753992 (2), 19088043 (1) (see all 9)
    glioma 27.9 15 17189382 (3), 17704802 (2), 19421150 (2), 9811337 (1) (see all 9)
    intrauterine growth retardation 27.4 1 19875484 (1)
    retinopathy 26.4 7 12815197 (2), 18408080 (1), 12506101 (1), 15548809 (1)

    GeneTests: TEK
    GeneReviews: TEK
    Genetic Association Database (GAD): TEK
    Human Genome Epidemiology (HuGE) Navigator: TEK (7 documents)

    Export disorders for TEK gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for TEK gene, integrated from 10 sources (see all 553):
    (articles sorted by number of sources associating them with TEK)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Mechanistic effects of autophosphorylation on receptor tyrosine kinase catalysis: enzymatic characterization of Tie2 and phospho- Tie2. (PubMed id 11513602)1, 2, 9 Murray B.W.... McTigue M.A. (Biochemistry 2001)
    2. Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium. (PubMed id 19223473)1, 2, 9 Yuan H.T.... Parikh S.M. (Mol. Cell. Biol. 2009)
    3. Tie2: a journey from normal angiogenesis to cancer and beyond. (PubMed id 18366015)1, 2, 9 Martin V.... Gomez-Manzano C. (Histol. Histopathol. 2008)
    4. The antiinflammatory endothelial tyrosine kinase Tie2 interacts with a novel nuclear factor-kappaB inhibitor ABIN-2. (PubMed id 12609966)1, 2, 9 Hughes D.P.... Brindle N.P. (Circ. Res. 2003)
    5. Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts. (PubMed id 18425119)1, 2, 9 Saharinen P.... Alitalo K. (Nat. Cell Biol. 2008)
    6. Biological characterization of angiopoietin-3 and angiopoietin-4. (PubMed id 15284220)1, 2, 9 Lee H.J.... Koh G.Y. (FASEB J. 2004)
    7. Structure of the Tie2 RTK domain: self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail. (PubMed id 11080633)1, 2, 9 Shewchuk L.M.... Moore J.T. (Structure 2000)
    8. Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells. (PubMed id 19116766)1, 2, 9 Yacyshyn O.K.... Stewart D.J. (Angiogenesis 2009)
    9. Somatic mutations in angiopoietin receptor gene TEK cause solitary and multiple sporadic venous malformations. (PubMed id 19079259)1, 4, 9 Limaye N....Vikkula M. (Nat. Genet. 2009)
    10. Hereditary cutaneomucosal venous malformations are caused by TIE2 mutations with widely variable hyper-phosphorylating effects. (PubMed id 19888299)1, 2, 9 Wouters V.... Vikkula M. (Eur. J. Hum. Genet. 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section

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    Entrez Gene: 7010 HGNC: 11724 AceView: TEK Ensembl:ENSG00000120156 euGenes: HUgn7010
    ECgene: TEK Kegg: 7010 H-InvDB: TEK

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for TEK Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for TEK Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=TEK[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for TEK gene:
    Search GeneIP for patents involving TEK

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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