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Q02858

- TIE2_MOUSE

UniProt

Q02858 - TIE2_MOUSE

Protein

Angiopoietin-1 receptor

Gene

Tek

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 148 (01 Oct 2014)
      Sequence version 2 (01 Feb 1995)
      Previous versions | rss
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    Functioni

    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 TIE1.7 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.1 PublicationPROSITE-ProRule annotation

    Enzyme regulationi

    Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-990 on the kinase activation loop.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei853 – 8531ATPPROSITE-ProRule annotation
    Active sitei962 – 9621Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi828 – 8369ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. protein tyrosine kinase activity Source: UniProtKB
    4. receptor activity Source: MGI
    5. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB-EC

    GO - Biological processi

    1. angiogenesis Source: UniProtKB
    2. cell-matrix adhesion Source: MGI
    3. endothelial cell proliferation Source: UniProtKB
    4. heart development Source: UniProtKB
    5. heart trabecula formation Source: UniProtKB
    6. hemopoiesis Source: MGI
    7. negative regulation of angiogenesis Source: UniProtKB
    8. negative regulation of apoptotic process Source: MGI
    9. negative regulation of endothelial cell apoptotic process Source: UniProtKB
    10. patterning of blood vessels Source: DFLAT
    11. peptidyl-tyrosine phosphorylation Source: UniProtKB
    12. positive regulation of angiogenesis Source: UniProtKB
    13. positive regulation of cell adhesion Source: MGI
    14. positive regulation of endothelial cell migration Source: UniProtKB
    15. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    16. positive regulation of focal adhesion assembly Source: UniProtKB
    17. positive regulation of intracellular signal transduction Source: UniProtKB
    18. positive regulation of peptidyl-serine phosphorylation Source: MGI
    19. positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
    20. positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
    21. positive regulation of protein kinase B signaling Source: UniProtKB
    22. positive regulation of protein phosphorylation Source: UniProtKB
    23. positive regulation of vascular endothelial growth factor receptor signaling pathway Source: DFLAT
    24. protein autophosphorylation Source: UniProtKB
    25. regulation of angiogenesis Source: MGI
    26. regulation of cell migration Source: MGI
    27. regulation of endothelial cell proliferation Source: DFLAT
    28. regulation of establishment or maintenance of cell polarity Source: UniProtKB
    29. response to retinoic acid Source: BHF-UCL
    30. single organismal cell-cell adhesion Source: MGI
    31. sprouting angiogenesis Source: UniProtKB
    32. substrate adhesion-dependent cell spreading Source: UniProtKB
    33. Tie signaling pathway Source: UniProtKB
    34. transmembrane receptor protein tyrosine kinase signaling pathway Source: UniProtKB
    35. vasculogenesis Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 3474.
    ReactomeiREACT_211860. Tie2 Signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Angiopoietin-1 receptor (EC:2.7.10.1)
    Alternative name(s):
    Endothelial tyrosine kinase
    HYK
    STK1
    Tunica interna endothelial cell kinase
    Tyrosine kinase with Ig and EGF homology domains-2
    Tyrosine-protein kinase receptor TEK
    Tyrosine-protein kinase receptor TIE-2
    Short name:
    mTIE2
    p140 TEK
    CD_antigen: CD202b
    Gene namesi
    Name:Tek
    Synonyms:Hyk, Tie-2, Tie2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 4

    Organism-specific databases

    MGIiMGI:98664. Tek.

    Subcellular locationi

    Cell membrane; Single-pass type I membrane protein. Cell junction By similarity. Cell junctionfocal adhesion By similarity. Cytoplasmcytoskeleton By similarity. Secreted By similarity
    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 By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-KW
    2. cytoskeleton Source: UniProtKB-SubCell
    3. extracellular region Source: UniProtKB-SubCell
    4. focal adhesion Source: UniProtKB-SubCell
    5. integral component of membrane Source: MGI
    6. integral component of plasma membrane Source: InterPro
    7. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Secreted

    Pathology & Biotechi

    Disruption phenotypei

    Embryonically lethal. Embryos die at about 10 dpc, due to strongly decreased numbers of blood vessel endothelial cells, leading to severe hemorrhaging, and due to defects in heart trabeculae development. Mice display a general malformation of the vascular network with defective sprouting and dilated blood vessels.2 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi853 – 8531K → A: Loss of kinase activity. 2 Publications
    Mutagenesisi1100 – 11001Y → F: Reduced levels of autophosphorylation. Abolishes interaction with GRB2 and GRB7. Abolishes phosphorylation of GRB7 and PIK3R1. 3 Publications
    Mutagenesisi1106 – 11061Y → F: Reduced levels of autophosphorylation. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2222By similarityAdd
    BLAST
    Chaini23 – 11221100Angiopoietin-1 receptorPRO_0000024475Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi44 ↔ 102By similarity
    Glycosylationi140 – 1401N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi158 – 1581N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi211 ↔ 220By similarity
    Disulfide bondi224 ↔ 233By similarity
    Disulfide bondi227 ↔ 240By similarity
    Disulfide bondi242 ↔ 251By similarity
    Disulfide bondi255 ↔ 264By similarity
    Disulfide bondi268 ↔ 274By similarity
    Disulfide bondi280 ↔ 287By similarity
    Disulfide bondi289 ↔ 298By similarity
    Disulfide bondi302 ↔ 311By similarity
    Disulfide bondi315 ↔ 323By similarity
    Disulfide bondi317 ↔ 329By similarity
    Disulfide bondi331 ↔ 340By similarity
    Disulfide bondi370 ↔ 424By similarity
    Glycosylationi399 – 3991N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi438 – 4381N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi464 – 4641N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi558 – 5581N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi595 – 5951N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi648 – 6481N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi690 – 6901N-linked (GlcNAc...)Sequence Analysis
    Modified residuei858 – 8581Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei990 – 9901Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1100 – 11001Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei1106 – 11061Phosphotyrosine; by autocatalysis2 Publications

    Post-translational modificationi

    Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2).By similarity
    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-990 in the kinase activation loop is phosphorylated first, followed by autophosphorylation at Tyr-1106 and at additional tyrosine residues. ANGPT1-induced phosphorylation is impaired during hypoxia, due to increased expression of ANGPT2 By similarity. Phosphorylation is important for interaction with GRB14, PIK3R1 and PTPN11. Phosphorylation at Tyr-1100 is important for interaction with GRB2 and GRB7. Phosphorylation at Tyr-1106 is important for interaction with DOK2 and for coupling to downstream signal transduction pathways in endothelial cells. Dephosphorylated by PTPRB.By similarity2 Publications
    Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation By similarity.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ02858.
    PRIDEiQ02858.

    PTM databases

    PhosphoSiteiQ02858.

    Expressioni

    Tissue specificityi

    Specifically expressed in developing vascular endothelial cells. Abundantly expressed in lung and heart, moderately in brain, liver and kidney, and weakly in thymus, spleen and testis.1 Publication

    Developmental stagei

    Expression detectable in day 8.5 embryos.

    Gene expression databases

    ArrayExpressiQ02858.
    BgeeiQ02858.
    CleanExiMM_TEK.
    GenevestigatoriQ02858.

    Interactioni

    Subunit structurei

    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 (tyrosine phosphorylated) with TNIP2. Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain) By similarity. 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.By similarity7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Grb2Q606313EBI-7099626,EBI-1688
    Grb7Q031603EBI-7099626,EBI-7100053

    Protein-protein interaction databases

    DIPiDIP-6050N.
    IntActiQ02858. 7 interactions.
    MINTiMINT-4137861.

    Structurei

    3D structure databases

    ProteinModelPortaliQ02858.
    SMRiQ02858. Positions 23-534, 811-1119.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini23 – 746724ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini768 – 1122355CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei747 – 76721HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini44 – 12380Ig-like C2-type 1Add
    BLAST
    Domaini210 – 25243EGF-like 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini254 – 29946EGF-like 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini301 – 34141EGF-like 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini350 – 44091Ig-like C2-type 2Add
    BLAST
    Domaini444 – 53996Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini543 – 63593Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini640 – 73394Fibronectin type-III 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini822 – 1094273Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The soluble extracellular domain is functionally active in angiopoietin binding and can modulate the activity of the membrane-bound form by competing for angiopoietins.By similarity

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. Tie subfamily.PROSITE-ProRule annotation
    Contains 3 EGF-like domains.PROSITE-ProRule annotation
    Contains 3 fibronectin type-III domains.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00750000117500.
    HOGENOMiHOG000049232.
    HOVERGENiHBG007316.

    Family and domain databases

    Gene3Di2.60.40.10. 5 hits.
    InterProiIPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR002049. EGF_laminin.
    IPR003961. Fibronectin_type3.
    IPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR018941. Tyr_kin_Tie2_Ig-like_dom-1_N.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view]
    PfamiPF00041. fn3. 3 hits.
    PF10430. Ig_Tie2_1. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view]
    PRINTSiPR00109. TYRKINASE.
    SMARTiSM00181. EGF. 1 hit.
    SM00180. EGF_Lam. 1 hit.
    SM00060. FN3. 3 hits.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF49265. SSF49265. 2 hits.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00022. EGF_1. 3 hits.
    PS01186. EGF_2. 3 hits.
    PS50026. EGF_3. 1 hit.
    PS50853. FN3. 3 hits.
    PS50835. IG_LIKE. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q02858-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDSLAGLVLC GVSLLLYGVV EGAMDLILIN SLPLVSDAET SLTCIASGWH     50
    PHEPITIGRD FEALMNQHQD PLEVTQDVTR EWAKKVVWKR EKASKINGAY 100
    FCEGRVRGQA IRIRTMKMRQ QASFLPATLT MTVDRGDNVN ISFKKVLIKE 150
    EDAVIYKNGS FIHSVPRHEV PDILEVHLPH AQPQDAGVYS ARYIGGNLFT 200
    SAFTRLIVRR CEAQKWGPDC SRPCTTCKNN GVCHEDTGEC ICPPGFMGRT 250
    CEKACEPHTF GRTCKERCSG PEGCKSYVFC LPDPYGCSCA TGWRGLQCNE 300
    ACPSGYYGPD CKLRCHCTNE EICDRFQGCL CSQGWQGLQC EKEGRPRMTP 350
    QIEDLPDHIE VNSGKFNPIC KASGWPLPTS EEMTLVKPDG TVLQPNDFNY 400
    TDRFSVAIFT VNRVLPPDSG VWVCSVNTVA GMVEKPFNIS VKVLPEPLHA 450
    PNVIDTGHNF AIINISSEPY FGDGPIKSKK LFYKPVNQAW KYIEVTNEIF 500
    TLNYLEPRTD YELCVQLARP GEGGEGHPGP VRRFTTASIG LPPPRGLSLL 550
    PKSQTALNLT WQPIFTNSED EFYVEVERRS LQTTSDQQNI KVPGNLTSVL 600
    LSNLVPREQY TVRARVNTKA QGEWSEELRA WTLSDILPPQ PENIKISNIT 650
    DSTAMVSWTI VDGYSISSII IRYKVQGKNE DQHIDVKIKN ATVTQYQLKG 700
    LEPETTYHVD IFAENNIGSS NPAFSHELRT LPHSPASADL GGGKMLLIAI 750
    LGSAGMTCIT VLLAFLIMLQ LKRANVQRRM AQAFQNREEP AVQFNSGTLA 800
    LNRKAKNNPD PTIYPVLDWN DIKFQDVIGE GNFGQVLKAR IKKDGLRMDA 850
    AIKRMKEYAS KDDHRDFAGE LEVLCKLGHH PNIINLLGAC EHRGYLYLAI 900
    EYAPHGNLLD FLRKSRVLET DPAFAIANST ASTLSSQQLL HFAADVARGM 950
    DYLSQKQFIH RDLAARNILV GENYIAKIAD FGLSRGQEVY VKKTMGRLPV 1000
    RWMAIESLNY SVYTTNSDVW SYGVLLWEIV SLGGTPYCGM TCAELYEKLP 1050
    QGYRLEKPLN CDDEVYDLMR QCWREKPYER PSFAQILVSL NRMLEERKTY 1100
    VNTTLYEKFT YAGIDCSAEE AA 1122
    Length:1,122
    Mass (Da):125,701
    Last modified:February 1, 1995 - v2
    Checksum:iF879623D103FFE96
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti161 – 17111FIHSVPRHEVP → LHPLSAPGMKYL in BAA02883. (PubMed:1282811)CuratedAdd
    BLAST
    Sequence conflicti538 – 5381S → C in CAA47857. (PubMed:8386827)Curated
    Sequence conflicti736 – 7361A → G in CAA47857. (PubMed:8386827)Curated
    Sequence conflicti736 – 7361A → G in AAB28663. (PubMed:8217221)Curated
    Sequence conflicti745 – 76117MLLIA…TCITV → DATHSHPWVWNDFASPC in BAA02883. (PubMed:1282811)CuratedAdd
    BLAST
    Sequence conflicti786 – 7861N → NV in BAA02883. (PubMed:1282811)Curated
    Sequence conflicti786 – 7861N → NV no nucleotide entry (PubMed:8395828)Curated
    Sequence conflicti913 – 9131R → G in BAA02883. (PubMed:1282811)Curated
    Sequence conflicti925 – 9317AIANSTA → CHRQQYS in BAA02883. (PubMed:1282811)Curated
    Sequence conflicti1117 – 11171S → P in BAA02883. (PubMed:1282811)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X71426 mRNA. Translation: CAA50557.1.
    X67553 mRNA. Translation: CAA47857.1.
    D13738 mRNA. Translation: BAA02883.1.
    S67051 mRNA. Translation: AAB28663.1.
    CCDSiCCDS71421.1.
    PIRiI54237.
    JH0771.
    JN0712.
    RefSeqiNP_001277478.1. NM_001290549.1.
    UniGeneiMm.14313.

    Genome annotation databases

    EnsembliENSMUST00000071168; ENSMUSP00000071162; ENSMUSG00000006386.
    GeneIDi21687.
    UCSCiuc008tsk.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X71426 mRNA. Translation: CAA50557.1 .
    X67553 mRNA. Translation: CAA47857.1 .
    D13738 mRNA. Translation: BAA02883.1 .
    S67051 mRNA. Translation: AAB28663.1 .
    CCDSi CCDS71421.1.
    PIRi I54237.
    JH0771.
    JN0712.
    RefSeqi NP_001277478.1. NM_001290549.1.
    UniGenei Mm.14313.

    3D structure databases

    ProteinModelPortali Q02858.
    SMRi Q02858. Positions 23-534, 811-1119.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-6050N.
    IntActi Q02858. 7 interactions.
    MINTi MINT-4137861.

    Chemistry

    BindingDBi Q02858.
    ChEMBLi CHEMBL5199.

    PTM databases

    PhosphoSitei Q02858.

    Proteomic databases

    PaxDbi Q02858.
    PRIDEi Q02858.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000071168 ; ENSMUSP00000071162 ; ENSMUSG00000006386 .
    GeneIDi 21687.
    UCSCi uc008tsk.1. mouse.

    Organism-specific databases

    MGIi MGI:98664. Tek.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00750000117500.
    HOGENOMi HOG000049232.
    HOVERGENi HBG007316.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 3474.
    Reactomei REACT_211860. Tie2 Signaling.

    Miscellaneous databases

    PROi Q02858.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q02858.
    Bgeei Q02858.
    CleanExi MM_TEK.
    Genevestigatori Q02858.

    Family and domain databases

    Gene3Di 2.60.40.10. 5 hits.
    InterProi IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR002049. EGF_laminin.
    IPR003961. Fibronectin_type3.
    IPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR018941. Tyr_kin_Tie2_Ig-like_dom-1_N.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view ]
    Pfami PF00041. fn3. 3 hits.
    PF10430. Ig_Tie2_1. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view ]
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00181. EGF. 1 hit.
    SM00180. EGF_Lam. 1 hit.
    SM00060. FN3. 3 hits.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 2 hits.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS00022. EGF_1. 3 hits.
    PS01186. EGF_2. 3 hits.
    PS50026. EGF_3. 1 hit.
    PS50853. FN3. 3 hits.
    PS50835. IG_LIKE. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Tie-1 and tie-2 define another class of putative receptor tyrosine kinase genes expressed in early embryonic vascular system."
      Sato T.N., Qin Y., Kozak C.A., Andus K.L.
      Proc. Natl. Acad. Sci. U.S.A. 90:9355-9358(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: BALB/c.
      Tissue: Lung.
    2. "The endothelial-specific receptor tyrosine kinase, tek, is a member of a new subfamily of receptors."
      Dumont D.J., Gradwol G.J., Fong G.-H., Auerbach R., Breitman M.L.
      Oncogene 8:1293-1301(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: CD-1.
      Tissue: Embryonic heart.
    3. "A novel tyrosine kinase, hyk, expressed in murine embryonic stem cells."
      Horita K., Yagi T., Kohmura N., Tomooka Y., Ikawa Y., Aizawa S.
      Biochem. Biophys. Res. Commun. 189:1747-1753(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Embryonic stem cell.
    4. "Tie2, a putative protein tyrosine kinase from a new class of cell surface receptor."
      Runting A.S., Stacker S.A., Wilks A.F.
      Growth Factors 9:99-105(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Lung.
    5. "Expression of tie-2, a member of a novel family of receptor tyrosine kinases, in the endothelial cell lineage."
      Schnuerch H., Risau W.
      Development 119:957-968(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    6. "Molecular cloning and characterization of mouse TIE and TEK receptor tyrosine kinase genes and their expression in hematopoietic stem cells."
      Iwama A., Hamaguchi I., Hashiyama M., Murayama Y., Yasunaga K., Suda T.
      Biochem. Biophys. Res. Commun. 195:301-309(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Tissue: Hematopoietic stem cell.
    7. "Tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors."
      Dumont D.J., Yamaguchi T.P., Conlon R.A., Rossant J., Breitman M.L.
      Oncogene 7:1471-1480(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 822-1122.
      Strain: CD-1.
      Tissue: Embryonic heart.
    8. "Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo."
      Dumont D.J., Gradwohl G., Fong G.H., Puri M.C., Gertsenstein M., Auerbach A., Breitman M.L.
      Genes Dev. 8:1897-1909(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, MUTAGENESIS OF LYS-853, CATALYTIC ACTIVITY, FUNCTION.
    9. "Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation."
      Sato T.N., Tozawa Y., Deutsch U., Wolburg-Buchholz K., Fujiwara Y., Gendron-Maguire M., Gridley T., Wolburg H., Risau W., Qin Y.
      Nature 376:70-74(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    10. "Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt."
      Kontos C.D., Stauffer T.P., Yang W.P., York J.D., Huang L., Blanar M.A., Meyer T., Peters K.G.
      Mol. Cell. Biol. 18:4131-4140(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PIK3R1, MUTAGENESIS OF TYR-1100, FUNCTION IN ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE AND AKT1.
    11. "Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration."
      Jones N., Master Z., Jones J., Bouchard D., Gunji Y., Sasaki H., Daly R., Alitalo K., Dumont D.J.
      J. Biol. Chem. 274:30896-30905(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GRB2; GRB7, GRB14, PTPN11/SHP2 AND PIK3R1, FUNCTION IN PHOSPHORYLATION OF GRB7 AND PIK3R1, MUTAGENESIS OF TYR-1100.
    12. "Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the angiopoietin receptor Tie-2."
      Fachinger G., Deutsch U., Risau W.
      Oncogene 18:5948-5953(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPRB.
    13. "Rescue of the early vascular defects in Tek/Tie2 null mice reveals an essential survival function."
      Jones N., Voskas D., Master Z., Sarao R., Jones J., Dumont D.J.
      EMBO Rep. 2:438-445(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: ANTI-APOPTOTIC FUNCTION.
    14. "Angiopoietin-1 and angiopoietin-2 share the same binding domains in the Tie-2 receptor involving the first Ig-like loop and the epidermal growth factor-like repeats."
      Fiedler U., Krissl T., Koidl S., Weiss C., Koblizek T., Deutsch U., Martiny-Baron G., Marme D., Augustin H.G.
      J. Biol. Chem. 278:1721-1727(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ANGPT1 AND ANGPT2, DOMAIN.
    15. "A unique autophosphorylation site on Tie2/Tek mediates Dok-R phosphotyrosine binding domain binding and function."
      Jones N., Chen S.H., Sturk C., Master Z., Tran J., Kerbel R.S., Dumont D.J.
      Mol. Cell. Biol. 23:2658-2668(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-1100 AND TYR-1106, MUTAGENESIS OF LYS-853; TYR-1100 AND TYR-1106, FUNCTION IN DOK2 PHOSPHORYLATION, INTERACTION WITH DOK2.
    16. "Biological characterization of angiopoietin-3 and angiopoietin-4."
      Lee H.J., Cho C.H., Hwang S.J., Choi H.H., Kim K.T., Ahn S.Y., Kim J.H., Oh J.L., Lee G.M., Koh G.Y.
      FASEB J. 18:1200-1208(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS ANGPT4 RECEPTOR AND IN ACTIVATION OF AKT1, INTERACTION WITH ANGPT4, AUTOPHOSPHORYLATION.
    17. Cited for: INTERACTION WITH PTPRB.
    18. "Tyrosine phosphorylation of Grb14 by Tie2."
      Sturk C., Dumont D.J.
      Cell Commun. Signal. 8:30-30(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GRB14, FUNCTION IN GRB14 PHOSPHORYLATION.

    Entry informationi

    Entry nameiTIE2_MOUSE
    AccessioniPrimary (citable) accession number: Q02858
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: February 1, 1995
    Last modified: October 1, 2014
    This is version 148 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3