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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

TEK Gene

protein-coding   GIFtS: 73
GCID: GC09P027109

TEK tyrosine kinase, endothelial

(Previous names: venous malformations, multiple cutaneous and mucosal )
(Previous symbol: VMCM)
 Explore 97 diseases affiliated with
TEK via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for TEK    

Aliases
for TEK gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
TEK Tyrosine Kinase, Endothelial1 2     P140 TEK2 3
TIE21 2 3 5     EC 2.7.10.13 8
VMCM1 2 3 5     CD202b1
VMCM11 2 3     Venous Malformations, Multiple Cutaneous And Mucosal1
TIE-21 2     CD202B2
Endothelial Tyrosine Kinase2 3     Angiopoietin-1 Receptor2
Tunica Interna Endothelial Cell Kinase2 3     Soluble TIE2 Variant 12
Tyrosine Kinase With Ig And EGF Homology Domains-22 3     Soluble TIE2 Variant 22
Tyrosine-Protein Kinase Receptor TEK2 3     CD202b Antigen3
Tyrosine-Protein Kinase Receptor TIE-22 3     EC 2.7.108
HTIE21     

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


Summaries
for TEK gene

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section
Entrez Gene summary for TEK:
The TEK receptor tyrosine kinase is expressed almost exclusively in endothelial cells in mice, rats, and humans. This
receptor possesses a unique extracellular domain containing 2 immunoglobulin-like loops separated by 3 epidermal
growth factor-like repeats that are connected to 3 fibronectin type III-like repeats. The ligand for the receptor is
angiopoietin-1. Defects in TEK are associated with inherited venous malformations; the TEK signaling pathway appears
to be critical for endothelial cell-smooth muscle cell communication in venous morphogenesis. TEK is closely related
to the TIE receptor tyrosine kinase. (provided by RefSeq, Jul 2008)

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)


Genomic Views
for TEK 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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000009.11  NC_018920.1  NT_008413.18  
Regulatory elements:
   SABiosciences 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 plasmid: TEK promoter sequence
   Search SABiosciences Chromatin IP Primers for TEK

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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

Proteins
for TEK gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
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)
Subcellular location: 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
6/9 PDB 3D structures from and Proteopedia for TEK (see all 9):
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

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
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q02763

    • 4/13 DME Specific Peptides for TEK (Q02763) (see all 13)
     NCDDEVY  FTYAGID  RDLAARN  QCWREKP 

    TEK Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_000450.2  
    ENSEMBL proteins: 
     ENSP00000430686   ENSP00000369375   ENSP00000430233   ENSP00000383977   ENSP00000428337  
    Reactome Protein details: Q02763
    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: TEK
    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
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Uscn

    Gene Ontology (GO): 5/14 cellular component terms (GO ID links to tree view) (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



    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: TEK
    OriGene Custom Antibody Services for TEK 
    GenScript Custom Superior Antibodies Services for TEK
    Novus Biologicals TEK Antibodies
    Abcam antibodies for TEK 
    Browse Antibodies at Uscn
    ThermoFisher Antibody for TEK

    Assay Products for TEK: 
    EMD Millipore Kits and Assays for the Analysis of TEK
    OriGene Custom Immunoassay Development
    Browse OriGene Fluorogenic Cell Assay Kits
    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 and CLIAs at Uscn

    Protein Domains /
    Families
    for TEK gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    TEK for domains           About GeneDecksing

    5/12 InterPro domains/families (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 families:
    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


    Function
    for TEK gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         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
    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

    miRNA
    Products:            		 OriGene 3'-UTR Clone: TEK
    Browse MicroRNA Expression Plasmids
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TEK
    8/14 QIAGEN miScript miRNA 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 plasmid: TEK 3' UTR sequence
    Inhib. RNA
    Products:            		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for TEK (see all 7)
    OriGene shRNA RFP: TEK
    OriGene siRNA: TEK
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TEK

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

    Clone
    Products:             		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for TEK (see all 5)
    OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for TEK (see all 2)
    OriGene custom cloning services – gene synthesis, subcloning, mutagenesis, variant library, vector shuttling 
    GenScript: all cDNA clones in your preferred vector: TEK (NM_000459)
    Browse Sino Biological Human cDNA Clones
    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
    Search LifeMap BioReagents cell lines for TEK

    In Situ Assay
    Products:       
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TEK

    Gene Ontology (GO): 5/6 molecular function terms (GO ID links to tree view) (see all 6):    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 IPI--


    TEK for ontologies           About GeneDecksing


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

    Animal Models:
         Mouse knock-outs for TEK: Tektm1Sato Tektm1Dmt
         9 MGI mutant phenotypes (inferred from 3 alleles) (MGI details for Tek):
     cardiovascular system  cellular  embryogenesis  growth/size  hematopoietic system 
     homeostasis/metabolism  mortality/aging  muscle  nervous system 

    TEK for phenotypes           About GeneDecksing


    Pathways & Interactions
    for TEK gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/19 super-pathways (see all 19) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1GPCR Pathway
    		GPCR Pathway1.00
    		Estrogen Pathway0.55
    		Ras Pathway0.62
    		Pancreatic Adenocarcinoma0.55
    		Breast Cancer Regulation by Stathmin10.58
    		Paxillin Interactions0.53
    		NFAT in Immune Response0.58
    		P2Y Receptor Signaling0.38
    2Rho Family GTPases
    		Rho Family GTPases1.00
    		MAPK Signaling0.51
    		ERK Signaling0.61
    		ILK Signaling0.45
    		Molecular Mechanisms of Cancer0.51
    3Nanog in Mammalian ESC Pluripotency
    		Nanog in Mammalian ESC Pluripotency1.00
    		14-3-3 Induced Intracellular Signaling0.59
    		GSK3 Signaling0.61
    		eNOS Signaling0.48
    4Development_PDGF signaling via STATs and NF-kB
    		Development_Angiopoietin - Tie2 signaling0.38
    		Angiopoietin-TIE2 Signaling0.13
    		Development Angiopoietin - Tie2 signaling0.38
    		Angiopoietin receptor Tie2-mediated signaling0.11
    5Actin Nucleation by ARP-WASP Complex
    		Actin Nucleation by ARP-WASP Complex1.00
    		CDC42 Pathway0.34
    		Actin Nucleation and Branching0.66

    Pathway sources
    See GeneCards unified pathways
    Show all pathways

    2 EMD Millipore Pathways for TEK
        Development Angiopoietin - Tie2 signaling
    G-protein signaling H-RAS regulation pathway

    5/32 Downloadable PowerPoint Slides of QIAGEN 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

    3        Reactome Pathways for TEK
        Hemostasis
    Cell surface interactions at the vascular wall
    Tie2 Signaling


    1         Kegg Pathway  (Kegg details for TEK):
        Rheumatoid arthritis


    TEK for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for TEK

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

    5/54 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): 5/43 biological process terms (GO ID links to tree view) (see all 43):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001525angiogenesis ISS--
    GO:0001934positive regulation of protein phosphorylation IMP18425120
    GO:0001935endothelial cell proliferation ISS--
    GO:0001938positive regulation of endothelial cell proliferation TAS18425120
    GO:0002040sprouting angiogenesis IMP14665640


    TEK for ontologies           About GeneDecksing



    Drugs & Compounds
    for TEK gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    TEK for compounds           About GeneDecksing

    EMD Millipore small molecules for TEK:
    Small Molecule - inhibitor
    Enzo Life Sciences drugs & compounds for TEK

    Browse Tocris compounds for TEK

    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--

    1 DrugBank Compound 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

    10/16 Novoseek 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)

    Search CenterWatch for drugs/clinical trials and news about TEK / TIE2 

    Transcripts
    for TEK gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section
    REFSEQ mRNAs for TEK gene: 
    NM_000459.3  

    Unigene Cluster for TEK:

    TEK tyrosine kinase, endothelial
    Hs.89640  [show with all ESTs]
    Unigene Representative Sequence: NM_000459
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000519097(uc010mjc.1) ENST00000380036(uc011lnn.1 uc003zqi.4 uc011lno.2 uc011lnp.2)
    ENST00000488798 ENST00000406359(uc003zqj.1) ENST00000519080

    miRNA
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    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TEK
    8/14 QIAGEN miScript miRNA 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 plasmid: TEK 3' UTR sequence
    Inhib. RNA
    Products:             		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for TEK (see all 7)
    OriGene shRNA RFP: TEK
    OriGene siRNA: TEK
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TEK
    Clone
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    GenScript: all cDNA clones in your preferred vector: TEK (NM_000459)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TEK 
    Primer
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    Additional cDNA 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 

    24/37 AceView cDNA sequences (see all 37):

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

    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

    Expression
    for TEK gene

    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    TEK expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: AGTGAATAAA

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    TEK expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    10/14 LifeMap In Vivo Development Anatomical Compartments/Cells (see all 14) 
    Tissue Anatomical Compartment CellCategory (developmental path)
    HeartAtrioventricular CanalEndocardial Tube CellsEndocardium
    HeartEndocardiumEndocardial CellsEndocardium
    HeartOutflow TractEndocardial Tube CellsEndocardium
    Lateral Plate MesodermEmbryonic Capillary PlexusAngioblastsEndothelium
    Lateral Plate MesodermProepicardiumAngioblastsEndothelium
    Neural TubePerineural capillary PlexusAngioblastsBlood Brain Barrier, Endothelium
    BoneBone MarrowHematopoietic Stem CellsBlood
    Extraembryonic MesodermExtraembryonic Blood IslandsExtraembryonic AngioblastsEndothelium
    HeartCardiac CrescentCardiac Crescent CellsMyocardium
    HeartCardinal VeinsVenous Endothelial CellsEndothelium
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization
    Stem Cell Differentiation: 10/19 LifeMap Cells (see all 19) 
    NameCategory
    PureStem™ endothelial progenitor 30-MV2-12 (Embryonic Progenitor Cell)Blood, Endothelium
    PureStem™ endothelial Progenitor 30-SM2-3 (Embryonic Progenitor Cell)Blood, Endothelium
    Endothelial progenitor cells (Adult Stem / Progenitor Cell)Endothelium
    Human umbilical vein endothelial cells (HUVEC) (Primary Cell)Endothelium
    PureStem™ endothelial progenitor 30-SM2-1 (Embryonic Progenitor Cell)Endothelium
    PureStem™ endothelial progenitor RP1-MV2-18 (Embryonic Progenitor Cell)Endothelium
    PureStem™ endothelial progenitor 30-MV2-14 (Embryonic Progenitor Cell)Endothelium
    Bone marrow-derived adherent progenitor cells (MultiStem) (Adult Stem / Progenitor Cell)Bone
    PureStem™ mesenchymal progenitor SM30 (Embryonic Progenitor Cell)Adipose, Bone, Cartilage
    PureStem™ progenitor E69 (Embryonic Progenitor Cell)

    See TEK Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for TEK

    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

        SABiosciences Expression via Pathway-Focused 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

    Primer
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    In Situ
    Assay Products:     
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TEK

    Orthologs
    for TEK gene

    (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)
    About This Section
    This gene was present in the common ancestor of chordates.

    Orthologs for TEK gene from 4/16 species (see all 16)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    chicken
    (Gallus gallus)    		 Aves TEK1 TEK tyrosine kinase, endothelial 71.59(n)
    74(a)    		   427368  XM_424944.3  XP_424944.3 
    lizard
    (Anolis carolinensis)    		 Reptilia TEK6
    		 --
    		 71(a)
    		 1 ↔ 1
    		 2(58847837-58887899)
    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 


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

    Paralogs
    for TEK gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for TEK gene
    AXL2  TIE12  MET2  RYK2  TYRO32  MERTK2  MST1R2  
    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    TIE    CSK    RYK    FGFR3
    DKFZp434L0319    KIT    TYRO3

    TEK for paralogs           About GeneDecksing



    Genomic Variants
    for TEK gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/2890 NCBI SNPs in TEK are shown (see all 2890)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 9 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs803389091,2
    		Cpathogenic44571195(+) AGGCTA/CCTTGT 2 Y S mis10--------
    rs803389081,2
    		Cpathogenic44577153(+) GGTTAC/TGGATG 2 R W mis10--------
    rs109677161,2
    		C,F,H,--27059879(+) GCACCC/TACCGA 1 -- us2k119Minor allele frequency- T:0.12NS EA NA WA 2480
    rs70418771,2
    		C,--27060423(+) ccaaaG/Ttgctg 1 -- us2k11Minor allele frequency- T:0.50WA 2
    rs70304241,2
    		C,F,H,--27060531(+) CTTTTT/CAGTAG 1 -- us2k16Minor allele frequency- C:0.02NS EA WA 538
    rs774554431,2
    		--27060770(+) CTGAGC/TCAGTA 1 -- us2k11Minor allele frequency- T:0.01NA 120
    rs769229801,2
    		F,--27060865(+) ATCGAT/CGTGAT 1 -- us2k11Minor allele frequency- C:0.10WA 118
    rs109677181,2
    		H,--27061043(+) TAAGTG/ATAGGG 1 -- us2k14Minor allele frequency- A:0.00NS EA 418
    rs575335441,2
    		C,--27061115(+) CTCTTC/TGCTCT 1 -- us2k11Minor allele frequency- T:0.50WA 2
    rs1117016531,2
    		C,--27061142(+) ATCCCA/GATCTA 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for TEK (27109139 - 27230173 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 2 variations for TEK
         2 CNVs: 52779 70534
    Human Gene Mutation Database (HGMD): TEK

    SABiosciences Cancer Mutation PCR Assays
    QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing TEK
    DNA2.0 Custom Variant and Variant Library Synthesis for TEK

    Disorders / Diseases
    for TEK gene

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

    OMIM gene information: 600221   
    OMIM disorders: 600195  
    UniProtKB/Swiss-Prot: TIE2_HUMAN, Q02763
  • Defects in TEK are a cause of dominantly inherited venous malformations (VMCM) [MIM:600195]; an error of
    • vascular morphogenesis characterized by dilated, serpiginous channels
  • Note=May play a role in a range of diseases with a vascular component, including neovascularization of tumors,
    • psoriasis and inflammation

    20/97 diseases for TEK (see all 97):    About MalaCards
    venous malformations    klippel-trenaunay syndrome    multiple cutaneous and mucosal venous malformations    tufted angioma
    placenta accreta    arteriovenous malformation    glomuvenous malformations    corneal neovascularization
    non-small cell lung carcinoma    critical limb ischemia    intermittent claudication    acute myocardial infarction
    capillary hemangioma    inflammatory bowel disease    myocardial infarction    congestive heart failure
    placental insufficiency    cavernous hemangioma    gastrointestinal stromal tumor    renal clear cell carcinoma

    10/65 Novoseek 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
    Multiple Cutaneous and Mucosal Venous Malformations

    Human Genome Epidemiology (HuGE) Navigator: TEK (7 documents)

    Export disorders for TEK gene to outside databases

    Publications
    for TEK gene

    (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)
    About This Section

    PubMed articles for TEK gene, integrated from 9 sources (see all 532):
    (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. (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. (2009)
    3. Tie2: a journey from normal angiogenesis to cancer and beyond. (PubMed id 18366015)1, 2, 9 Martin V....Gomez-Manzano C. (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. (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. (2008)
    6. Biological characterization of angiopoietin-3 and angiopoietin-4. (PubMed id 15284220)1, 2, 9 Lee H.J....Koh G.Y. (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. (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. (2009)
    9. Hereditary cutaneomucosal venous malformations are ca used by TIE2 mutations with widely variable hyper-phosphorylating effects. (PubMed id 19888299)1, 2, 9 Wouters V....Vikkula M. (2010)
    10. Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells. (PubMed id 14665640)1, 2, 9 Audero E....Bussolino F. (2004)

    External Searches for TEK gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing TEK gene

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 7010 HGNC: 11724 AceView: TEK Ensembl:ENSG00000120156 euGenes: HUgn7010
    ECgene: TEK Kegg: 7010 H-InvDB: TEK

    Other Databases showing TEK gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing TEK gene

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    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/sites/GeneTests/lab/gene/TEK

    Intellectual Property
    for TEK gene

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    		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



    Products
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    Advanced Cell Diagnostics
    About This Section

     EMD Millipore Kits and Assays for the Analysis of TEK
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