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DrugBank target: Q02763

DrugBank target: Q02763 (TIE2_HUMAN)     

Example structure of target: 1fvr

( There are 11 structures corresponding to this UniProt sequence in the PDB. Click the orange, plus icon above for a list. )

Angiopoietin-1 receptor

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, p140 TEK, hTIE2.

Function

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

Enzyme

2.7.10.1   [EC->PDB]   [IntEnz]   [ExPASy]   [KEGG]  

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Disease(s)

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

Schematic diagram of Pfam domains in target sequence plus wiring diagrams of PDB structures of target.

1fvr
2gy5
2gy7
2oo8
   more ...

Key:    PfamA domain

Sequence length: 1123 a.a.

Approved drugs targeting this protein

The DrugBank database identifies 3 drugs for this target protein:

 

 
Generic name: DB08896 regorafenib
Formula: C21H15Clf4N4O3
Structure: There are no structures of this molecule in the PDB.
Generic name: DB08901 ponatinib
0LI
Formula: C29H27F3N6O
Structure: There are 4 PDB structures containing this molecule although none are bound to the above target protein.
Generic name: DB05294 vandetanib
ZD6
Formula: C22H24Brfn4O2
Structure: There is one PDB structure containing this molecule but it is not bound to the above target protein.

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