Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

TEK (Q02763) - Overview - Molecular Target Synopsis

Protein


TEK, Angiopoietin-1 receptor
Enzyme Classification 2.7.10.1
UniProt Q02763

Also Known as TIE2_HUMAN, TEK, TIE2, VMCM, VMCM1

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. 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).

6MWE
CRYSTAL STRUCTURE OF TIE2 IN COMPLEX WITH DECIPERA COMPOUND DP1919
RCSB/PDB
Inspect Structure
See all 3D Structures for TEK

Isoforms / Transcripts (Protein Coding)


Drugs


TEK is targeted by Approved Drug Vandetanib. (see details)
Vandetanib

Sub-cellular localization


UniProt: TEK is active in the following subcellular-locations: cell junction, cell membrane, cytoplasm, cytoskeleton, focal adhesion, secreted.
GO terms: TEK is active in the following subcellular-locations: apical plasma membrane, basal plasma membrane, basolateral plasma membrane, cell surface, cell-cell junction, cytoplasm, extracellular region, focal adhesion, integral component of plasma membrane, membrane raft, microtubule organizing center, microvillus, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TEK has gain in 3 cell-lines, loss in 35 cell-lines and no signal in 967 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, SK_OV_3, NCI_H460

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H522, Hs 675.T, OCI-M2

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: AG445, HUVEC, SK-N-SH

(see details)

RNA Interference


TEK was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: H23, MIAPACA2. (see details)

3D Structures


For TEK there are:
15 structures (21 chains) solved
12 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TEK has been screened with 1704 compounds (2860 bioactivities), 399 compounds have bioactivities that show binding affinity of <= 500nM (668 bioactivities). (see details)