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Q02763

- TIE2_HUMAN

UniProt

Q02763 - TIE2_HUMAN

Protein

Angiopoietin-1 receptor

Gene

TEK

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 168 (01 Oct 2014)
      Sequence version 2 (16 Dec 2008)
      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 TIE1.10 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.6 PublicationsPROSITE-ProRule annotation

    Enzyme regulationi

    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.6 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei855 – 8551ATPCurated
    Active sitei964 – 9641Proton acceptor1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi830 – 8389ATPCurated

    GO - Molecular functioni

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

    GO - Biological processi

    1. angiogenesis Source: UniProtKB
    2. blood coagulation Source: Reactome
    3. cell-cell signaling Source: ProtInc
    4. cell-matrix adhesion Source: Ensembl
    5. definitive hemopoiesis Source: UniProtKB
    6. endochondral ossification Source: Ensembl
    7. endothelial cell proliferation Source: UniProtKB
    8. glomerulus vasculature development Source: UniProtKB
    9. heart development Source: UniProtKB
    10. heart trabecula formation Source: UniProtKB
    11. intracellular signal transduction Source: Ensembl
    12. leukocyte migration Source: Reactome
    13. negative regulation of angiogenesis Source: UniProtKB
    14. negative regulation of apoptotic process Source: UniProtKB
    15. negative regulation of endothelial cell apoptotic process Source: UniProtKB
    16. negative regulation of inflammatory response Source: UniProtKB
    17. organ regeneration Source: Ensembl
    18. peptidyl-tyrosine phosphorylation Source: UniProtKB
    19. positive regulation of actin cytoskeleton reorganization Source: UniProtKB
    20. positive regulation of angiogenesis Source: UniProtKB
    21. positive regulation of endothelial cell migration Source: UniProtKB
    22. positive regulation of endothelial cell proliferation Source: UniProtKB
    23. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    24. positive regulation of focal adhesion assembly Source: UniProtKB
    25. positive regulation of intracellular signal transduction Source: UniProtKB
    26. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
    27. positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
    28. positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
    29. positive regulation of protein kinase B signaling Source: UniProtKB
    30. positive regulation of protein phosphorylation Source: UniProtKB
    31. protein autophosphorylation Source: UniProtKB
    32. protein oligomerization Source: UniProtKB
    33. regulation of endothelial cell apoptotic process Source: UniProtKB
    34. regulation of establishment or maintenance of cell polarity Source: UniProtKB
    35. regulation of vascular permeability Source: UniProtKB
    36. response to cAMP Source: Ensembl
    37. response to estrogen Source: Ensembl
    38. response to hypoxia Source: Ensembl
    39. response to peptide hormone Source: Ensembl
    40. signal transduction Source: ProtInc
    41. single organismal cell-cell adhesion Source: Ensembl
    42. sprouting angiogenesis Source: UniProtKB
    43. substrate adhesion-dependent cell spreading Source: UniProtKB
    44. Tie signaling pathway Source: UniProtKB
    45. transmembrane receptor protein tyrosine kinase signaling pathway Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Angiogenesis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 2681.
    ReactomeiREACT_12621. Tie2 Signaling.
    SignaLinkiQ02763.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Angiopoietin-1 receptor (EC:2.7.10.1)
    Alternative name(s):
    Endothelial tyrosine kinase
    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:
    hTIE2
    p140 TEK
    CD_antigen: CD202b
    Gene namesi
    Name:TEK
    Synonyms:TIE2, VMCM, VMCM1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 9

    Organism-specific databases

    HGNCiHGNC:11724. TEK.

    Subcellular locationi

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

    GO - Cellular componenti

    1. apical plasma membrane Source: UniProtKB
    2. basal plasma membrane Source: UniProtKB
    3. basolateral plasma membrane Source: UniProtKB
    4. cell-cell junction Source: UniProtKB
    5. cell surface Source: UniProtKB
    6. cytoplasm Source: UniProtKB-KW
    7. cytoskeleton Source: UniProtKB-SubCell
    8. extracellular region Source: UniProtKB-SubCell
    9. focal adhesion Source: UniProtKB-SubCell
    10. integral component of plasma membrane Source: UniProtKB
    11. membrane raft Source: UniProtKB
    12. microvillus Source: UniProtKB
    13. plasma membrane Source: Reactome

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Involvement in diseasei

    Dominantly inherited venous malformations (VMCM) [MIM:600195]: An error of vascular morphogenesis characterized by dilated, serpiginous channels.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti849 – 8491R → W in VMCM; increased ligand-independent autophosphorylation and kinase activation. 3 Publications
    VAR_006352
    Natural varianti897 – 8971Y → C in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_066606
    Natural varianti897 – 8971Y → S in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_008716
    Natural varianti915 – 9151R → H in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_066607
    Natural varianti918 – 9181R → C in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_066608
    Natural varianti919 – 9191V → L in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_066609
    Natural varianti925 – 9251A → S in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_066610
    Natural varianti1100 – 11001K → N in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_066611
    May play a role in a range of diseases with a vascular component, including neovascularization of tumors, psoriasis and inflammation.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi855 – 8551K → R: Loss of kinase activity. 2 Publications
    Mutagenesisi1102 – 11021Y → F: Abolishes interaction with SHC1. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi600195. phenotype.
    Orphaneti2451. Mucocutaneous venous malformations.
    PharmGKBiPA36441.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 22221 PublicationAdd
    BLAST
    Chaini23 – 11241102Angiopoietin-1 receptorPRO_0000024474Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi44 ↔ 1021 Publication
    Glycosylationi140 – 1401N-linked (GlcNAc...)1 Publication
    Glycosylationi158 – 1581N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi211 ↔ 2201 Publication
    Disulfide bondi224 ↔ 2331 Publication
    Disulfide bondi227 ↔ 2401 Publication
    Disulfide bondi242 ↔ 2511 Publication
    Disulfide bondi255 ↔ 2641 Publication
    Disulfide bondi268 ↔ 2741 Publication
    Disulfide bondi280 ↔ 2871 Publication
    Disulfide bondi289 ↔ 2981 Publication
    Disulfide bondi302 ↔ 3111 Publication
    Disulfide bondi315 ↔ 3231 Publication
    Disulfide bondi317 ↔ 3291 Publication
    Disulfide bondi331 ↔ 3401 Publication
    Disulfide bondi370 ↔ 4241 Publication
    Glycosylationi399 – 3991N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi438 – 4381N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi464 – 4641N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi560 – 5601N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi596 – 5961N-linked (GlcNAc...)1 Publication
    Glycosylationi649 – 6491N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi691 – 6911N-linked (GlcNAc...)Sequence Analysis
    Modified residuei860 – 8601Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei992 – 9921Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei1102 – 11021Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei1108 – 11081Phosphotyrosine; by autocatalysis2 Publications

    Post-translational modificationi

    Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2).1 Publication
    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 PTPRB.2 Publications
    Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ02763.
    PRIDEiQ02763.

    PTM databases

    PhosphoSiteiQ02763.

    Expressioni

    Tissue specificityi

    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.2 Publications

    Gene expression databases

    ArrayExpressiQ02763.
    BgeeiQ02763.
    CleanExiHS_TEK.
    GenevestigatoriQ02763.

    Organism-specific databases

    HPAiCAB010359.
    HPA011738.

    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 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).13 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ANGPT2O151234EBI-2257090,EBI-2912111
    PTPN12Q052092EBI-2257090,EBI-2266035
    PTPRBP234673EBI-2257090,EBI-1265766
    PTPRCP085753EBI-2257090,EBI-1341
    PTPRJQ129132EBI-2257090,EBI-2264500
    PTPRKQ152622EBI-2257090,EBI-474052
    PTPROQ168272EBI-2257090,EBI-723739

    Protein-protein interaction databases

    BioGridi112869. 11 interactions.
    DIPiDIP-6047N.
    IntActiQ02763. 21 interactions.
    STRINGi9606.ENSP00000383977.

    Structurei

    Secondary structure

    1
    1124
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi26 – 294
    Beta strandi33 – 353
    Beta strandi40 – 467
    Beta strandi56 – 594
    Turni61 – 633
    Beta strandi64 – 663
    Beta strandi74 – 763
    Beta strandi80 – 889
    Beta strandi98 – 1069
    Beta strandi109 – 11911
    Beta strandi123 – 1253
    Beta strandi127 – 1337
    Beta strandi139 – 1457
    Beta strandi153 – 1575
    Beta strandi160 – 1656
    Helixi167 – 1693
    Beta strandi172 – 1787
    Helixi183 – 1853
    Beta strandi187 – 1937
    Helixi198 – 2003
    Beta strandi202 – 2087
    Beta strandi215 – 2173
    Turni235 – 2373
    Beta strandi246 – 2483
    Beta strandi259 – 2613
    Turni271 – 2766
    Beta strandi279 – 2813
    Turni282 – 2854
    Beta strandi286 – 2883
    Helixi296 – 2983
    Beta strandi322 – 3243
    Turni325 – 3273
    Beta strandi328 – 3303
    Beta strandi361 – 3666
    Beta strandi369 – 3735
    Helixi380 – 3823
    Beta strandi383 – 3864
    Beta strandi396 – 4005
    Beta strandi405 – 4084
    Beta strandi411 – 4144
    Helixi416 – 4183
    Beta strandi420 – 4289
    Beta strandi431 – 4399
    Beta strandi816 – 8183
    Helixi821 – 8233
    Beta strandi825 – 8317
    Helixi833 – 8353
    Beta strandi837 – 8459
    Beta strandi848 – 85811
    Helixi868 – 8769
    Beta strandi888 – 8947
    Beta strandi897 – 9026
    Helixi910 – 9156
    Helixi919 – 9224
    Helixi924 – 9296
    Beta strandi932 – 9365
    Helixi938 – 95720
    Helixi967 – 9693
    Beta strandi970 – 9723
    Helixi974 – 9763
    Beta strandi978 – 9803
    Beta strandi986 – 9894
    Turni1002 – 10043
    Helixi1007 – 10126
    Helixi1017 – 103216
    Turni1038 – 10414
    Helixi1044 – 10507
    Helixi1051 – 10533
    Helixi1065 – 107410
    Helixi1079 – 10813
    Helixi1085 – 109713
    Beta strandi1098 – 11003
    Helixi1118 – 11203

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1FVRX-ray2.20A/B808-1124[»]
    2GY5X-ray2.90A23-445[»]
    2GY7X-ray3.70B23-445[»]
    2OO8X-ray2.20X808-1124[»]
    2OSCX-ray2.80A808-1124[»]
    2P4IX-ray2.50A/B808-1124[»]
    2WQBX-ray2.95A802-1124[»]
    3BEAX-ray2.02A917-935[»]
    3L8PX-ray2.40A808-1124[»]
    4K0VX-ray4.51A23-542[»]
    ProteinModelPortaliQ02763.
    SMRiQ02763. Positions 23-631, 640-725, 813-1121.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ02763.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini23 – 748726ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini770 – 1124355CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei749 – 76921HelicalSequence 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
    Domaini447 – 54195Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini545 – 63692Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini641 – 73595Fibronectin type-III 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini824 – 1096273Protein 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.1 Publication

    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.
    HOGENOMiHOG000049232.
    HOVERGENiHBG007316.
    InParanoidiQ02763.
    KOiK05121.
    OMAiCHEDTGE.
    OrthoDBiEOG7966FR.
    PhylomeDBiQ02763.
    TreeFamiTF317568.

    Family and domain databases

    Gene3Di2.60.40.10. 6 hits.
    InterProiIPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    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. 2 hits.
    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]

    Sequences (3)i

    Sequence statusi: Complete.

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

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q02763-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MDSLASLVLC GVSLLLSGTV EGAMDLILIN SLPLVSDAET SLTCIASGWR     50
    PHEPITIGRD FEALMNQHQD PLEVTQDVTR EWAKKVVWKR EKASKINGAY 100
    FCEGRVRGEA IRIRTMKMRQ QASFLPATLT MTVDKGDNVN ISFKKVLIKE 150
    EDAVIYKNGS FIHSVPRHEV PDILEVHLPH AQPQDAGVYS ARYIGGNLFT 200
    SAFTRLIVRR CEAQKWGPEC NHLCTACMNN GVCHEDTGEC ICPPGFMGRT 250
    CEKACELHTF GRTCKERCSG QEGCKSYVFC LPDPYGCSCA TGWKGLQCNE 300
    ACHPGFYGPD CKLRCSCNNG EMCDRFQGCL CSPGWQGLQC EREGIQRMTP 350
    KIVDLPDHIE VNSGKFNPIC KASGWPLPTN EEMTLVKPDG TVLHPKDFNH 400
    TDHFSVAIFT IHRILPPDSG VWVCSVNTVA GMVEKPFNIS VKVLPKPLNA 450
    PNVIDTGHNF AVINISSEPY FGDGPIKSKK LLYKPVNHYE AWQHIQVTNE 500
    IVTLNYLEPR TEYELCVQLV RRGEGGEGHP GPVRRFTTAS IGLPPPRGLN 550
    LLPKSQTTLN LTWQPIFPSS EDDFYVEVER RSVQKSDQQN IKVPGNLTSV 600
    LLNNLHPREQ YVVRARVNTK AQGEWSEDLT AWTLSDILPP QPENIKISNI 650
    THSSAVISWT ILDGYSISSI TIRYKVQGKN EDQHVDVKIK NATITQYQLK 700
    GLEPETAYQV DIFAENNIGS SNPAFSHELV TLPESQAPAD LGGGKMLLIA 750
    ILGSAGMTCL TVLLAFLIIL QLKRANVQRR MAQAFQNVRE EPAVQFNSGT 800
    LALNRKVKNN PDPTIYPVLD WNDIKFQDVI GEGNFGQVLK ARIKKDGLRM 850
    DAAIKRMKEY ASKDDHRDFA GELEVLCKLG HHPNIINLLG ACEHRGYLYL 900
    AIEYAPHGNL LDFLRKSRVL ETDPAFAIAN STASTLSSQQ LLHFAADVAR 950
    GMDYLSQKQF IHRDLAARNI LVGENYVAKI ADFGLSRGQE VYVKKTMGRL 1000
    PVRWMAIESL NYSVYTTNSD VWSYGVLLWE IVSLGGTPYC GMTCAELYEK 1050
    LPQGYRLEKP LNCDDEVYDL MRQCWREKPY ERPSFAQILV SLNRMLEERK 1100
    TYVNTTLYEK FTYAGIDCSA EEAA 1124
    Length:1,124
    Mass (Da):125,830
    Last modified:December 16, 2008 - v2
    Checksum:iE739DEC3E4FEB124
    GO
    Isoform 2 (identifier: Q02763-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         300-342: Missing.

    Show »
    Length:1,081
    Mass (Da):121,048
    Checksum:iFA9BF050B49AB557
    GO
    Isoform 3 (identifier: Q02763-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         18-121: Missing.
         300-342: Missing.
         788-788: Missing.

    Show »
    Length:976
    Mass (Da):109,141
    Checksum:iCE8D06A4F93D48E0
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti536 – 5361F → L in BAG58094. (PubMed:14702039)Curated
    Sequence conflicti695 – 6951T → I in AAA61139. (PubMed:8382358)Curated
    Sequence conflicti939 – 9402QQ → HH in AAH35514. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti117 – 1171K → N in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. 2 Publications
    VAR_035714
    Natural varianti148 – 1481I → T.1 Publication
    Corresponds to variant rs35969327 [ dbSNP | Ensembl ].
    VAR_041855
    Natural varianti226 – 2261A → V.1 Publication
    Corresponds to variant rs35814893 [ dbSNP | Ensembl ].
    VAR_041856
    Natural varianti346 – 3461Q → P.4 Publications
    Corresponds to variant rs682632 [ dbSNP | Ensembl ].
    VAR_048002
    Natural varianti391 – 3911T → I.
    Corresponds to variant rs34032300 [ dbSNP | Ensembl ].
    VAR_048003
    Natural varianti486 – 4861V → I.1 Publication
    Corresponds to variant rs1334811 [ dbSNP | Ensembl ].
    VAR_024578
    Natural varianti600 – 6001V → L.1 Publication
    Corresponds to variant rs35030851 [ dbSNP | Ensembl ].
    VAR_041857
    Natural varianti634 – 6341L → F.1 Publication
    Corresponds to variant rs35378598 [ dbSNP | Ensembl ].
    VAR_041858
    Natural varianti676 – 6761V → I.1 Publication
    Corresponds to variant rs56367117 [ dbSNP | Ensembl ].
    VAR_041859
    Natural varianti724 – 7241A → T.1 Publication
    Corresponds to variant rs4631561 [ dbSNP | Ensembl ].
    VAR_041860
    Natural varianti849 – 8491R → W in VMCM; increased ligand-independent autophosphorylation and kinase activation. 3 Publications
    VAR_006352
    Natural varianti883 – 8831P → A in an ovarian serous carcinoma sample; somatic mutation. 1 Publication
    VAR_041861
    Natural varianti897 – 8971Y → C in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_066606
    Natural varianti897 – 8971Y → S in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_008716
    Natural varianti915 – 9151R → H in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_066607
    Natural varianti918 – 9181R → C in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_066608
    Natural varianti919 – 9191V → L in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_066609
    Natural varianti925 – 9251A → S in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_066610
    Natural varianti1100 – 11001K → N in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 Publication
    VAR_066611
    Natural varianti1124 – 11241A → V in a renal clear cell carcinoma sample; somatic mutation. 1 Publication
    VAR_041862

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei18 – 121104Missing in isoform 3. 1 PublicationVSP_042137Add
    BLAST
    Alternative sequencei300 – 34243Missing in isoform 2 and isoform 3. 1 PublicationVSP_042138Add
    BLAST
    Alternative sequencei788 – 7881Missing in isoform 3. 1 PublicationVSP_042139

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L06139 mRNA. Translation: AAA61139.1.
    AK291775 mRNA. Translation: BAF84464.1.
    AK294887 mRNA. Translation: BAG57981.1.
    AK295043 mRNA. Translation: BAG58094.1.
    AL133411, AL355432, AL355433 Genomic DNA. Translation: CAI16055.1.
    CH471071 Genomic DNA. Translation: EAW58571.1.
    CH471071 Genomic DNA. Translation: EAW58572.1.
    BC035514 mRNA. Translation: AAH35514.2.
    CCDSiCCDS6519.1. [Q02763-1]
    PIRiI58388.
    RefSeqiNP_000450.2. NM_000459.4.
    NP_001277006.1. NM_001290077.1.
    NP_001277007.1. NM_001290078.1.
    UniGeneiHs.89640.

    Genome annotation databases

    EnsembliENST00000380036; ENSP00000369375; ENSG00000120156. [Q02763-1]
    ENST00000406359; ENSP00000383977; ENSG00000120156. [Q02763-2]
    ENST00000519097; ENSP00000430686; ENSG00000120156. [Q02763-3]
    GeneIDi7010.
    KEGGihsa:7010.
    UCSCiuc003zqj.1. human. [Q02763-2]
    uc011lnp.2. human. [Q02763-3]

    Polymorphism databases

    DMDMi218511853.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L06139 mRNA. Translation: AAA61139.1 .
    AK291775 mRNA. Translation: BAF84464.1 .
    AK294887 mRNA. Translation: BAG57981.1 .
    AK295043 mRNA. Translation: BAG58094.1 .
    AL133411 , AL355432 , AL355433 Genomic DNA. Translation: CAI16055.1 .
    CH471071 Genomic DNA. Translation: EAW58571.1 .
    CH471071 Genomic DNA. Translation: EAW58572.1 .
    BC035514 mRNA. Translation: AAH35514.2 .
    CCDSi CCDS6519.1. [Q02763-1 ]
    PIRi I58388.
    RefSeqi NP_000450.2. NM_000459.4.
    NP_001277006.1. NM_001290077.1.
    NP_001277007.1. NM_001290078.1.
    UniGenei Hs.89640.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1FVR X-ray 2.20 A/B 808-1124 [» ]
    2GY5 X-ray 2.90 A 23-445 [» ]
    2GY7 X-ray 3.70 B 23-445 [» ]
    2OO8 X-ray 2.20 X 808-1124 [» ]
    2OSC X-ray 2.80 A 808-1124 [» ]
    2P4I X-ray 2.50 A/B 808-1124 [» ]
    2WQB X-ray 2.95 A 802-1124 [» ]
    3BEA X-ray 2.02 A 917-935 [» ]
    3L8P X-ray 2.40 A 808-1124 [» ]
    4K0V X-ray 4.51 A 23-542 [» ]
    ProteinModelPortali Q02763.
    SMRi Q02763. Positions 23-631, 640-725, 813-1121.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112869. 11 interactions.
    DIPi DIP-6047N.
    IntActi Q02763. 21 interactions.
    STRINGi 9606.ENSP00000383977.

    Chemistry

    BindingDBi Q02763.
    ChEMBLi CHEMBL2111375.
    GuidetoPHARMACOLOGYi 1842.

    PTM databases

    PhosphoSitei Q02763.

    Polymorphism databases

    DMDMi 218511853.

    Proteomic databases

    PaxDbi Q02763.
    PRIDEi Q02763.

    Protocols and materials databases

    DNASUi 7010.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000380036 ; ENSP00000369375 ; ENSG00000120156 . [Q02763-1 ]
    ENST00000406359 ; ENSP00000383977 ; ENSG00000120156 . [Q02763-2 ]
    ENST00000519097 ; ENSP00000430686 ; ENSG00000120156 . [Q02763-3 ]
    GeneIDi 7010.
    KEGGi hsa:7010.
    UCSCi uc003zqj.1. human. [Q02763-2 ]
    uc011lnp.2. human. [Q02763-3 ]

    Organism-specific databases

    CTDi 7010.
    GeneCardsi GC09P027109.
    GeneReviewsi TEK.
    HGNCi HGNC:11724. TEK.
    HPAi CAB010359.
    HPA011738.
    MIMi 600195. phenotype.
    600221. gene.
    neXtProti NX_Q02763.
    Orphaneti 2451. Mucocutaneous venous malformations.
    PharmGKBi PA36441.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000049232.
    HOVERGENi HBG007316.
    InParanoidi Q02763.
    KOi K05121.
    OMAi CHEDTGE.
    OrthoDBi EOG7966FR.
    PhylomeDBi Q02763.
    TreeFami TF317568.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 2681.
    Reactomei REACT_12621. Tie2 Signaling.
    SignaLinki Q02763.

    Miscellaneous databases

    ChiTaRSi TEK. human.
    EvolutionaryTracei Q02763.
    GeneWikii TEK_tyrosine_kinase.
    GenomeRNAii 7010.
    NextBioi 27384.
    PROi Q02763.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q02763.
    Bgeei Q02763.
    CleanExi HS_TEK.
    Genevestigatori Q02763.

    Family and domain databases

    Gene3Di 2.60.40.10. 6 hits.
    InterProi IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    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. 2 hits.
    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. "Molecular cloning and characterization of a novel receptor protein tyrosine kinase from human placenta."
      Ziegler S.F., Bird T.A., Schneringer J.A., Schooley K.A., Baum P.R.
      Oncogene 8:663-670(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, TISSUE SPECIFICITY, VARIANT PRO-346.
      Tissue: Placenta.
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), VARIANT PRO-346.
      Tissue: Brain and Placenta.
    3. "DNA sequence and analysis of human chromosome 9."
      Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
      , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
      Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT PRO-346.
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT PRO-346.
      Tissue: Pancreas.
    6. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
      Zhang Z., Henzel W.J.
      Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 23-37.
    7. Cited for: FUNCTION AS RECEPTOR FOR ANGPT1 AND ANGPT2, INTERACTION WITH ANGPT1 AND ANGPT2, AUTOPHOSPHORYLATION.
    8. "Identification of a soluble form of the angiopoietin receptor TIE-2 released from endothelial cells and present in human blood."
      Reusch P., Barleon B., Weindel K., Martiny-Baron G., Godde A., Siemeister G., Marme D.
      Angiogenesis 4:123-131(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, TISSUE SPECIFICITY.
    9. "Mechanistic effects of autophosphorylation on receptor tyrosine kinase catalysis: enzymatic characterization of Tie2 and phospho-Tie2."
      Murray B.W., Padrique E.S., Pinko C., McTigue M.A.
      Biochemistry 40:10243-10253(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT TYR-860; TYR-992 AND TYR-1108.
    10. "Tie-2-dependent activation of RhoA and Rac1 participates in endothelial cell motility triggered by angiopoietin-1."
      Cascone I., Audero E., Giraudo E., Napione L., Maniero F., Philips M.R., Collard J.G., Serini G., Bussolino F.
      Blood 102:2482-2490(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN REGULATION OF PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; ENDOTHELIAL CELL MIGRATION AND REORGANIZATION OF THE ACTIN CYTOSKELETON.
    11. "The antiinflammatory endothelial tyrosine kinase Tie2 interacts with a novel nuclear factor-kappaB inhibitor ABIN-2."
      Hughes D.P., Marron M.B., Brindle N.P.
      Circ. Res. 92:630-636(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TNIP2, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-855.
    12. "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 IN REGULATION OF ANGIOGENESIS; CELL SURVIVAL; CELL MIGRATION AND ACTIVATION OF AKT1, DOMAIN, INTERACTION WITH ANGPT1; ANGPT2 AND ANGPT4.
    13. "Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells."
      Audero E., Cascone I., Maniero F., Napione L., Arese M., Lanfrancone L., Bussolino F.
      J. Biol. Chem. 279:13224-13233(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS ANGPT1 RECEPTOR IN PHOSPHORYLATION OF SHC1 AND PIK3R1; REGULATION OF CELL MIGRATION AND ANGIOGENESIS, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-1102, PHOSPHORYLATION AT TYR-1102, CATALYTIC ACTIVITY, INTERACTION WITH SHC1.
    14. "Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2."
      Saharinen P., Kerkela K., Ekman N., Marron M., Brindle N., Lee G.M., Augustin H., Koh G.Y., Alitalo K.
      J. Cell Biol. 169:239-243(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TIE1, SUBCELLULAR LOCATION, FUNCTION AS RECEPTOR FOR ANGPT1 IN PHOSPHORYLATION OF TIE1, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-855.
    15. "Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1."
      Fukuhara S., Sako K., Minami T., Noda K., Kim H.Z., Kodama T., Shibuya M., Takakura N., Koh G.Y., Mochizuki N.
      Nat. Cell Biol. 10:513-526(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS ANGPT1 RECEPTOR IN ACTIVATION OF AKT1 OR MAPK1/ERK2 AND MAPK3/ERK1; REGULATION OF ENDOTHELIAL CELL MIGRATION AND CELL SPREADING, SUBCELLULAR LOCATION.
    16. "Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts."
      Saharinen P., Eklund L., Miettinen J., Wirkkala R., Anisimov A., Winderlich M., Nottebaum A., Vestweber D., Deutsch U., Koh G.Y., Olsen B.R., Alitalo K.
      Nat. Cell Biol. 10:527-537(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS ANGPT1 RECEPTOR IN ACTIVATION OF AKT1 OR MAPK1/ERK2 AND MAPK3/ERK1; REGULATION OF ENDOTHELIAL CELL MIGRATION AND REGULATION OF FOCAL ADHESION ASSEMBLY, INTERACTION WITH TIE1, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION.
    17. "Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells."
      Yacyshyn O.K., Lai P.F.H., Forse K., Teichert-Kuliszewska K., Jurasz P., Stewart D.J.
      Angiogenesis 12:25-33(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPRB.
    18. "Angiopoietin-1-induced ubiquitylation of Tie2 by c-Cbl is required for internalization and degradation."
      Wehrle C., Van Slyke P., Dumont D.J.
      Biochem. J. 423:375-380(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CBL, SUBCELLULAR LOCATION, UBIQUITINATION.
    19. Cited for: INTERACTION WITH PTPRB.
    20. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-596.
      Tissue: Liver.
    21. "Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium."
      Yuan H.T., Khankin E.V., Karumanchi S.A., Parikh S.M.
      Mol. Cell. Biol. 29:2011-2022(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS RECEPTOR FOR ANGPT1 AND ANGPT2 IN ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE AND AKT1; STIMULATION OF ENDOTHELIAL CELL SURVIVAL AND MIGRATION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION.
    22. "Tie2: a journey from normal angiogenesis to cancer and beyond."
      Martin V., Liu D., Fueyo J., Gomez-Manzano C.
      Histol. Histopathol. 23:773-780(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION; INTERACTION WITH EFFECTOR AND SCAFFOLDING PROTEINS, ROLE IN DISEASE.
    23. "Tie2 is tied at the cell-cell contacts and to extracellular matrix by angiopoietin-1."
      Fukuhara S., Sako K., Noda K., Nagao K., Miura K., Mochizuki N.
      Exp. Mol. Med. 41:133-139(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON SUBCELLULAR LOCATION AND CONTEXT-SPECIFIC SIGNALING.
    24. "Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system."
      Augustin H.G., Koh G.Y., Thurston G., Alitalo K.
      Nat. Rev. Mol. Cell Biol. 10:165-177(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    25. "Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis."
      Fukuhara S., Sako K., Noda K., Zhang J., Minami M., Mochizuki N.
      Histol. Histopathol. 25:387-396(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    26. "Targeting the ANGPT-TIE2 pathway in malignancy."
      Huang H., Bhat A., Woodnutt G., Lappe R.
      Nat. Rev. Cancer 10:575-585(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON SIGNALING, ENZYME REGULATION, ROLE IN DISEASE.
    27. "Structure of the Tie2 RTK domain: self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail."
      Shewchuk L.M., Hassell A.M., Ellis B., Holmes W.D., Davis R., Horne E.L., Kadwell S.H., McKee D.D., Moore J.T.
      Structure 8:1105-1113(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 808-1124, ACTIVE SITE, ENZYME REGULATION, PREDICTION OF ATP-BINDING REGION.
    28. "Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex."
      Barton W.A., Tzvetkova-Robev D., Miranda E.P., Kolev M.V., Rajashankar K.R., Himanen J.P., Nikolov D.B.
      Nat. Struct. Mol. Biol. 13:524-532(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 23-445 ALONE AND IN COMPLEX WITH ANGPT2, GLYCOSYLATION AT ASN-140, DISULFIDE BONDS.
    29. Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 808-1124 IN COMPLEX WITH TRIAZINE DERIVATIVE, ENZYME REGULATION.
    30. Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 808-1124 IN COMPLEX WITH TRIAZINE DERIVATIVE, ENZYME REGULATION.
    31. "Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with activity against Tie-2 in vitro and in vivo."
      Luke R.W., Ballard P., Buttar D., Campbell L., Curwen J., Emery S.C., Griffen A.M., Hassall L., Hayter B.R., Jones C.D., McCoull W., Mellor M., Swain M.L., Tucker J.A.
      Bioorg. Med. Chem. Lett. 19:6670-6674(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 802-1124 IN COMPLEX WITH THIAZOLOPYRIMIDINE DERIVATIVE, ENZYME REGULATION.
    32. "Crystal structure of cytoplasmic kinase domain of Tie2 complexed with inhibitor CEP11207."
      Fedorov A.A., Fedorov E.V., Pauletti D., Meyer S.L., Hudkins R.L., Almo S.C.
      Submitted (JAN-2010) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 808-1124 IN COMPLEX WITH CEP11207.
    33. "Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2."
      Vikkula M., Boon L.M., Carraway K.L. III, Calvert J.T., Diamonti A.J., Goumnerov B., Pasyk K.A., Marchuk D.A., Warman M.L., Cantley L.C., Mulliken J.B., Olse B.R.
      Cell 87:1181-1190(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT VMCM TRP-849.
    34. Cited for: VARIANTS VMCM TRP-849 AND SER-897.
    35. Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-117.
    36. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-117; THR-148; VAL-226; ILE-486; LEU-600; PHE-634; ILE-676; THR-724; ALA-883 AND VAL-1124.
    37. "Hereditary cutaneomucosal venous malformations are caused by TIE2 mutations with widely variable hyper-phosphorylating effects."
      Wouters V., Limaye N., Uebelhoer M., Irrthum A., Boon L.M., Mulliken J.B., Enjolras O., Baselga E., Berg J., Dompmartin A., Ivarsson S.A., Kangesu L., Lacassie Y., Murphy J., Teebi A.S., Penington A., Rieu P., Vikkula M.
      Eur. J. Hum. Genet. 18:414-420(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS VMCM TRP-849; CYS-897; HIS-915; CYS-918; LEU-919; SER-925 AND ASN-1100, CHARACTERIZATION OF VARIANTS VMCM TRP-849; SER-897; HIS-915; CYS-918; LEU-919; SER-925 AND ASN-1100.

    Entry informationi

    Entry nameiTIE2_HUMAN
    AccessioniPrimary (citable) accession number: Q02763
    Secondary accession number(s): A8K6W0
    , B4DH20, B4DHD3, D3DRK5, E7EWI2, Q5TCU2, Q8IV34
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: December 16, 2008
    Last modified: October 1, 2014
    This is version 168 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

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      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 9
      Human chromosome 9: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    8. SIMILARITY comments
      Index of protein domains and families

    External Data

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