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Q02763

- TIE2_HUMAN

UniProt

Q02763 - TIE2_HUMAN

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Protein
Angiopoietin-1 receptor
Gene
TEK, TIE2, VMCM, VMCM1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 Publications

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 – 8551ATP Inferred
Active sitei964 – 9641Proton acceptor Inferred

Regions

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

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

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.5 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 748726Extracellular Reviewed prediction
Add
BLAST
Transmembranei749 – 76921Helical; Reviewed prediction
Add
BLAST
Topological domaini770 – 1124355Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. apical plasma membrane Source: UniProtKB
  2. basal plasma membrane Source: UniProtKB
  3. basolateral plasma membrane Source: UniProtKB
  4. cell surface Source: UniProtKB
  5. cell-cell junction 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
Complete GO annotation...

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.
Note: The disease is caused by mutations affecting the gene represented in this entry.5 Publications
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. 2 Publications
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.2 Publications

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 Publication
Add
BLAST
Chaini23 – 11241102Angiopoietin-1 receptor
PRO_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...) Reviewed prediction
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...) Reviewed prediction
Glycosylationi438 – 4381N-linked (GlcNAc...) Reviewed prediction
Glycosylationi464 – 4641N-linked (GlcNAc...) Reviewed prediction
Glycosylationi560 – 5601N-linked (GlcNAc...) Reviewed prediction
Glycosylationi596 – 5961N-linked (GlcNAc...)1 Publication
Glycosylationi649 – 6491N-linked (GlcNAc...) Reviewed prediction
Glycosylationi691 – 6911N-linked (GlcNAc...) Reviewed prediction
Modified residuei860 – 8601Phosphotyrosine; by autocatalysis1 Publication
Modified residuei992 – 9921Phosphotyrosine; by autocatalysis1 Publication
Modified residuei1102 – 11021Phosphotyrosine; by autocatalysis1 Publication
Modified residuei1108 – 11081Phosphotyrosine; by autocatalysis1 Publication

Post-translational modificationi

Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2).
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.8 Publications
Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation.8 Publications

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).8 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. 20 interactions.
STRINGi9606.ENSP00000383977.

Structurei

Secondary structure

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.

Miscellaneous databases

EvolutionaryTraceiQ02763.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 12380Ig-like C2-type 1
Add
BLAST
Domaini210 – 25243EGF-like 1
Add
BLAST
Domaini254 – 29946EGF-like 2
Add
BLAST
Domaini301 – 34141EGF-like 3
Add
BLAST
Domaini350 – 44091Ig-like C2-type 2
Add
BLAST
Domaini447 – 54195Fibronectin type-III 1
Add
BLAST
Domaini545 – 63692Fibronectin type-III 2
Add
BLAST
Domaini641 – 73595Fibronectin type-III 3
Add
BLAST
Domaini824 – 1096273Protein kinase
Add
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

Contains 3 EGF-like domains.

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

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. 2 Publications
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.
VSP_042137Add
BLAST
Alternative sequencei300 – 34243Missing in isoform 2 and isoform 3.
VSP_042138Add
BLAST
Alternative sequencei788 – 7881Missing in isoform 3.
VSP_042139

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti536 – 5361F → L in BAG58094. 1 Publication
Sequence conflicti695 – 6951T → I in AAA61139. 1 Publication
Sequence conflicti939 – 9402QQ → HH in AAH35514. 1 Publication

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. 20 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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 167 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

  1. Human cell differentiation molecules
    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

Dasty 3

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