Names & Taxonomy

Uniprot ID:
Q02763
Entry Name:
TIE2_HUMAN
Status:
reviewed
Protein Names:
Angiopoietin-1 receptor (EC 2.7.10.1) (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) (hTIE2) (p140 TEK) (CD antigen CD202b)
Gene Names:
TEK TIE2 VMCM VMCM1
Gene Names Primary:
TEK
Organism:
Homo sapiens (Human)

Structure

Length:
1124
Sequence:
MDSLASLVLCGVSLLLSGTVEGAMDLILINSLPLVSDAETSLTCIASGWRPHEPITIGRDFEALMNQHQDPLEVTQDVTREWAKKVVWKREKASKINGAYFCEGRVRGEAIRIRTMKMRQQASFLPATLTMTVDKGDNVNISFKKVLIKEEDAVIYKNGSFIHSVPRHEVPDILEVHLPHAQPQDAGVYSARYIGGNLFTSAFTRLIVRRCEAQKWGPECNHLCTACMNNGVCHEDTGECICPPGFMGRTCEKACELHTFGRTCKERCSGQEGCKSYVFCLPDPYGCSCATGWKGLQCNEACHPGFYGPDCKLRCSCNNGEMCDRFQGCLCSPGWQGLQCEREGIQRMTPKIVDLPDHIEVNSGKFNPICKASGWPLPTNEEMTLVKPDGTVLHPKDFNHTDHFSVAIFTIHRILPPDSGVWVCSVNTVAGMVEKPFNISVKVLPKPLNAPNVIDTGHNFAVINISSEPYFGDGPIKSKKLLYKPVNHYEAWQHIQVTNEIVTLNYLEPRTEYELCVQLVRRGEGGEGHPGPVRRFTTASIGLPPPRGLNLLPKSQTTLNLTWQPIFPSSEDDFYVEVERRSVQKSDQQNIKVPGNLTSVLLNNLHPREQYVVRARVNTKAQGEWSEDLTAWTLSDILPPQPENIKISNITHSSAVISWTILDGYSISSITIRYKVQGKNEDQHVDVKIKNATITQYQLKGLEPETAYQVDIFAENNIGSSNPAFSHELVTLPESQAPADLGGGKMLLIAILGSAGMTCLTVLLAFLIILQLKRANVQRRMAQAFQNVREEPAVQFNSGTLALNRKVKNNPDPTIYPVLDWNDIKFQDVIGEGNFGQVLKARIKKDGLRMDAAIKRMKEYASKDDHRDFAGELEVLCKLGHHPNIINLLGACEHRGYLYLAIEYAPHGNLLDFLRKSRVLETDPAFAIANSTASTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRGQEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYDLMRQCWREKPYERPSFAQILVSLNRMLEERKTYVNTTLYEKFTYAGIDCSAEEAA
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell membrane; Single-pass type I membrane protein. Cell junction. Cell junction, focal adhesion. Cytoplasm, cytoskeleton. 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.

Function

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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:
ENZYME REGULATION: 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.
Active Site:
ACT_SITE 964 964 Proton acceptor.
Cross Reference Drug Bank:
DB00415 DB08901 DB08896 DB05294
Gene Ontology Go:
apical plasma membrane
basal plasma membrane
basolateral plasma membrane
cell surface
cell-cell junction
cytoplasm
cytoskeleton
extracellular region
focal adhesion
integral component of plasma membrane
membrane raft
microvillus
plasma membrane
ATP binding
protein kinase activity
protein tyrosine kinase activity
receptor activity
transmembrane receptor protein tyrosine kinase activity
activation of MAPKK activity
angiogenesis
axon guidance
blood coagulation
cell-cell signaling
definitive hemopoiesis
endochondral ossification
endothelial cell proliferation
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
glomerulus vasculature development
heart development
heart trabecula formation
innate immune response
insulin receptor signaling pathway
leukocyte migration
MAPK cascade
negative regulation of angiogenesis
negative regulation of apoptotic process
negative regulation of endothelial cell apoptotic process
negative regulation of inflammatory response
neurotrophin TRK receptor signaling pathway
organ regeneration
peptidyl-tyrosine phosphorylation
positive regulation of actin cytoskeleton reorganization
positive regulation of angiogenesis
positive regulation of endothelial cell migration
positive regulation of endothelial cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of focal adhesion assembly
positive regulation of intracellular signal transduction
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of phosphatidylinositol 3-kinase signaling
positive regulation of protein kinase B signaling
positive regulation of protein phosphorylation
protein autophosphorylation
protein oligomerization
Ras protein signal transduction
regulation of endothelial cell apoptotic process
regulation of establishment or maintenance of cell polarity
regulation of vascular permeability
response to cAMP
response to estrogen
response to hypoxia
signal transduction
small GTPase mediated signal transduction
sprouting angiogenesis
substrate adhesion-dependent cell spreading
Tie signaling pathway
transmembrane receptor protein tyrosine kinase signaling pathway
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Biological Process:
activation of MAPKK activity
angiogenesis
axon guidance
blood coagulation
cell-cell signaling
definitive hemopoiesis
endochondral ossification
endothelial cell proliferation
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
glomerulus vasculature development
heart development
heart trabecula formation
innate immune response
insulin receptor signaling pathway
leukocyte migration
MAPK cascade
negative regulation of angiogenesis
negative regulation of apoptotic process
negative regulation of endothelial cell apoptotic process
negative regulation of inflammatory response
neurotrophin TRK receptor signaling pathway
organ regeneration
peptidyl-tyrosine phosphorylation
positive regulation of actin cytoskeleton reorganization
positive regulation of angiogenesis
positive regulation of endothelial cell migration
positive regulation of endothelial cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of focal adhesion assembly
positive regulation of intracellular signal transduction
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of phosphatidylinositol 3-kinase signaling
positive regulation of protein kinase B signaling
positive regulation of protein phosphorylation
protein autophosphorylation
protein oligomerization
Ras protein signal transduction
regulation of endothelial cell apoptotic process
regulation of establishment or maintenance of cell polarity
regulation of vascular permeability
response to cAMP
response to estrogen
response to hypoxia
signal transduction
small GTPase mediated signal transduction
sprouting angiogenesis
substrate adhesion-dependent cell spreading
Tie signaling pathway
transmembrane receptor protein tyrosine kinase signaling pathway
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Molecular Function:
ATP binding
protein kinase activity
protein tyrosine kinase activity
receptor activity
transmembrane receptor protein tyrosine kinase activity
Gene Ontology Cellular Component:
apical plasma membrane
basal plasma membrane
basolateral plasma membrane
cell-cell junction
cell surface
cytoplasm
cytoskeleton
extracellular region
focal adhesion
integral component of plasma membrane
membrane raft
microvillus
plasma membrane
Keywords:
3D-structure
ATP-binding
Alternative splicing
Angiogenesis
Cell junction
Cell membrane
Complete proteome
Cytoplasm
Cytoskeleton
Direct protein sequencing
Disease mutation
Disulfide bond
EGF-like domain
Glycoprotein
Immunoglobulin domain
Kinase
Membrane
Nucleotide-binding
Phosphoprotein
Polymorphism
Receptor
Reference proteome
Repeat
Secreted
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Ubl conjugation
Interacts With:
O15123; Q05209; P23467; P08575; Q12913; Q15262; Q16827

Publication

PubMed ID:
8382358 14702039 15164053 15489334 15340161 9204896 11806244 11513602 12816861 12609966 15284220 14665640 15851516 18425120 18425119 19116766 19689429 19451274 19159218 19223473 18366015 19293632 19234476 20054809 20651738 11080633 16732286 17350837 17253678 19854647 8980225 10369874 16959974 17344846 19888299