Tclin TEK Angiopoietin-1 receptor

Protein Summary

Description

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. This gene encodes a receptor that belongs to the protein tyrosine kinase Tie2 family. The encoded protein possesses a unique extracellular region that contains two immunoglobulin-like domains, three epidermal growth factor (EGF)-like domains and three fibronectin type III repeats. The ligand angiopoietin-1 binds to this receptor and mediates a signaling pathway that functions in embryonic vascular development. Mutations in this gene are associated with inherited venous malformations of the skin and mucous membranes. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

Uniprot Accession IDs

• Q02763
• A8K6W0
• B4DH20
• B4DHD3
• D3DRK5
• E7EWI2
• Q5TCU2
• Q8IV34

Gene Name

• TEK

Ensembl ID

• ENST00000380036
• ENSP00000369375
• ENSG00000120156
• ENST00000406359
• ENSP00000383977
• ENST00000519097
• ENSP00000430686

Symbol

• TIE2
• VMCM
• VMCM1
• TIE2
• VMCM
• GLC3E
• TIE-2
• VMCM1
• CD202B

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
protein domain	1
molecular function	0.98
transcription factor perturbation	0.96
gene perturbation	0.91

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Tie Family / Angiopoietin-1 Receptor

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1199.03   (req: < 5)

Gene RIFs: 197   (req: <= 3)

Antibodies: 1276   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1199.03   (req: >= 5)

Gene RIFs: 197   (req: > 3)

Antibodies: 1276   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 50

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 248

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 4

Protein Sequence and Structure

Residue Counts

Protein Sequence

Find Targets by Sequence

Show Full Sequence

ProtVista Viewer

Expression Data (0 Tissues)

tutorial

No expression data found

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

Go To Tool

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

Go To Tool

GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

Go To Tool

GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

Go To Tool

ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

Go To Tool

Approved Drugs (4)

Explore Approved Drugs

1 – 4 of 4

sorafenib

TEKTclin Kinase

INHIBITOR pKd : 7.8

crizotinib

TEKTclin Kinase

INHIBITOR pKi : 9.13

regorafenib

TEKTclin Kinase

INHIBITOR pIC50 : 9.3

cabozantinib

TEKTclin Kinase

INHIBITOR pIC50 : 8.89

Active Ligands (248)

Explore Active Ligands

1 – 10 of 248

TAE-684

TEKTclin Kinase

pKi : 8.5

foretinib

TEKTclin Kinase

pKd : 7.92

AST-487

TEKTclin Kinase

pKd : 7.77

CHEMBL1784637

TEKTclin Kinase

pIC50 : 9.7

linifanib

TEKTclin Kinase

pKi : 7.06

doramapimod

TEKTclin Kinase

pKd : 7.7

DDR1/2 inhibitor 5n

TEKTclin Kinase

pKd : 7.96

pexmetinib

TEKTclin Kinase

pKd : 6.17

CP-547632

TEKTclin Kinase

pKd : 8.4

CEP-11981

TEKTclin Kinase

pIC50 : 8.52

Protein-Protein Interactions (215)

Explore Interacting Targets

1 – 10 of 215

• See Interactions on String-DB

ANGPT2

Tbio

Novelty:  0.00116183

Score:  0.999

Data Source:  Reactome,STRINGDB

ANGPT1

Tbio

Novelty:  0.00115408

Score:  0.999

Data Source:  Reactome,STRINGDB

ANGPT4

Tbio

Novelty:  0.02566013

Score:  0.978

Data Source:  Reactome,STRINGDB

VEGFA

Tclin

Novelty:  0.0000378

Score:  0.968

Data Source:  STRINGDB

GRB14

Tbio

Novelty:  0.02565119

Score:  0.967

Data Source:  Reactome,STRINGDB

GRB2

Tchem

Novelty:  0.00091605

Score:  0.959

Data Source:  Reactome,STRINGDB

DOK2

Tbio

Novelty:  0.02651438

Score:  0.957

Data Source:  Reactome,STRINGDB

PTPN11

Tchem

Family:  Enzyme

Novelty:  0.00073124

Score:  0.955

Data Source:  Reactome,STRINGDB

SHC1

Tchem

Novelty:  0.00083615

Score:  0.953

Data Source:  Reactome,STRINGDB

MMP2

Tchem

Family:  Enzyme

Novelty:  0.00012762

Score:  0.95

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (186)

Reactome (12)

KEGG (6)

PathwayCommons (3)

WikiPathways (165)

Cell surface interactions at the vascular wall (R-HSA-202733)

Click on a row in the table to change the structure displayed.

Find Similar Targets

Items per page:

5

1 – 5 of 12

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cell surface interactions at the vascular wall	211 targets	R-HSA-202733
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	FLT3 Signaling	264 targets	R-HSA-9607240
Reactome	Hemostasis	666 targets	R-HSA-109582
Reactome	Immune System	2246 targets	R-HSA-168256

Name	Explore in Pharos	Explore in Source
Cell surface interactions at the vascular wall	211 targets	R-HSA-202733
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
FLT3 Signaling	264 targets	R-HSA-9607240
Hemostasis	666 targets	R-HSA-109582
Immune System	2246 targets	R-HSA-168256

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (64)

Functions (8)

Components (14)

Processes (42)

Find Similar Targets

Items per page:

10

1 – 8 of 8

GO Term	Evidence	Assigned by
protein tyrosine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
transmembrane receptor protein tyrosine kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
transmembrane signaling receptor activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
protein kinase activity	Traceable Author Statement (TAS)	ProtInc
Ras guanyl-nucleotide exchange factor activity	Traceable Author Statement (TAS)	Reactome
signaling receptor activity	Traceable Author Statement (TAS)	ProtInc
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
growth factor binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (8)

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 8

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
angiopoietin-1 receptor measurement	EFO_0010600	1	2	2		96
endothelial growth factor measurement	EFO_0006900	1	1	1		85.7
hepatocyte growth factor measurement	EFO_0006903	1	1	1		85.7
angiopoietin-2 receptor measurement	EFO_0006902	1	1	1		85.7
angiopoietin-2 measurement	EFO_0006901	1	1	1		85.7

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 8

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
angiopoietin-1 receptor measurement	EFO_0010600	2		96
endothelial growth factor measurement	EFO_0006900	1		85.7
hepatocyte growth factor measurement	EFO_0006903	1		85.7
angiopoietin-2 receptor measurement	EFO_0006902	1		85.7
angiopoietin-2 measurement	EFO_0006901	1		85.7

Reset Zoom  Beta Count   Odds Ratio

Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Angiogenesis
ATP-binding
Cell junction
Cell membrane
Complete proteome
Cytoplasm
Cytoskeleton
Direct protein sequencing

GWAS Trait Find Similar Targets

No Header	No Header
angiopoietin-1 receptor measurement
angiopoietin-2 measurement
angiopoietin-2 receptor measurement
asthma
blood protein measurement
endothelial growth factor measurement
heel bone mineral density
hepatocyte growth factor measurement

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
embryo phenotype
growth/size/body region phenotype
hematopoietic system phenotype
mortality/aging
muscle phenotype
nervous system phenotype

IDG Resources

No IDG generated resources found

Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	TEK receptor tyrosine kinase	VGNC:10114	465028
Macaque	TEK receptor tyrosine kinase		707455
Mouse	TEK receptor tyrosine kinase	MGI:98664	21687
Rat	TEK receptor tyrosine kinase	RGD:620980	89804
Dog	TEK receptor tyrosine kinase	VGNC:47241	403714

Species	Name	OMA	EggNOG	Inparanoid
Chimp	TEK receptor tyrosine kinase
Macaque	TEK receptor tyrosine kinase
Mouse	TEK receptor tyrosine kinase
Rat	TEK receptor tyrosine kinase
Dog	TEK receptor tyrosine kinase

Publication Statistics

PubMed Score 1199.03

PubMed score by year

Reset Zoom

PubTator Score 706.74

PubTator score by year

Reset Zoom

Patents

Patents by year

Reset Zoom

Related Publications

Text Mined References (237)

GeneRif Annotations (197)

Items per page:

10

0 of 0

PMID	Year	Title