Tek
entrez
21687
canonical
uniprot
Q02858
canonical
ensembl
ENSMUSG00000006386
resolver
ensp
ENSMUSP00000071162
resolver
ensp
ENSMUSP00000073595
resolver
ensp
ENSMUSP00000099862
resolver
enst
ENSMUST00000071168
resolver
enst
ENSMUST00000073939
resolver
enst
ENSMUST00000102798
resolver
genesymbol
Tek
resolver
genesymbol_syn
Hyk
resolver
genesymbol_syn
Tie-2
resolver
genesymbol_syn
Tie2
resolver
uniprot
B1AWS8
resolver
uniprot
F7AEA0
resolver
uniprot
Q80YS4
resolver
uniprot_entry
B1AWS8_MOUSE
resolver
uniprot_entry
F7AEA0_MOUSE
resolver
uniprot_entry
Q80YS4_MOUSE
resolver
uniprot_entry
TIE2_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-990 on the kinase activation loop. {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MDSLAGLVLCGVSLLLYGVVEGAMDLILINSLPLVSDAETSLTCIASGWHPHEPITIGRDFEALMNQHQDPLEVTQDVTREWAKKVVWKREKASKINGAYFCEGRVRGQAIRIRTMKMRQQASFLPATLTMTVDRGDNVNISFKKVLIKEEDAVIYKNGSFIHSVPRHEVPDILEVHLPHAQPQDAGVYSARYIGGNLFTSAFTRLIVRRCEAQKWGPDCSRPCTTCKNNGVCHEDTGECICPPGFMGRTCEKACEPHTFGRTCKERCSGPEGCKSYVFCLPDPYGCSCATGWRGLQCNEACPSGYYGPDCKLRCHCTNEEICDRFQGCLCSQGWQGLQCEKEGRPRMTPQIEDLPDHIEVNSGKFNPICKASGWPLPTSEEMTLVKPDGTVLQPNDFNYTDRFSVAIFTVNRVLPPDSGVWVCSVNTVAGMVEKPFNISVKVLPEPLHAPNVIDTGHNFAIINISSEPYFGDGPIKSKKLFYKPVNQAWKYIEVTNEIFTLNYLEPRTDYELCVQLARPGEGGEGHPGPVRRFTTASIGLPPPRGLSLLPKSQTALNLTWQPIFTNSEDEFYVEVERRSLQTTSDQQNIKVPGNLTSVLLSNLVPREQYTVRARVNTKAQGEWSEELRAWTLSDILPPQPENIKISNITDSTAMVSWTIVDGYSISSIIIRYKVQGKNEDQHIDVKIKNATVTQYQLKGLEPETTYHVDIFAENNIGSSNPAFSHELRTLPHSPASADLGGGKMLLIAILGSAGMTCITVLLAFLIMLQLKRANVQRRMAQAFQNREEPAVQFNSGTLALNRKAKNNPDPTIYPVLDWNDIKFQDVIGEGNFGQVLKARIKKDGLRMDAAIKRMKEYASKDDHRDFAGELEVLCKLGHHPNIINLLGACEHRGYLYLAIEYAPHGNLLDFLRKSRVLETDPAFAIANSTASTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYIAKIADFGLSRGQEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYDLMRQCWREKPYERPSFAQILVSLNRMLEERKTYVNTTLYEKFTYAGIDCSAEEAA
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
FUNCTION: Tyrosine-protein kinase that acts as a 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 pro-inflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for postnatal 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. {ECO:0000269|PubMed:10521483, ECO:0000269|PubMed:12665569, ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:20973951, ECO:0000269|PubMed:7596437, ECO:0000269|PubMed:7958865, ECO:0000269|PubMed:9632797}.
uniprot
proteins
mass_dalton
125701
uniprot
proteins
mutagenesis
MUTAGEN 853; /note="K->A: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:12665569, ECO:0000269|PubMed:7958865"; MUTAGEN 1100; /note="Y->F: Reduced levels of autophosphorylation. Abolishes interaction with GRB2 and GRB7. Abolishes phosphorylation of GRB7 and PIK3R1."; /evidence="ECO:0000269|PubMed:10521483, ECO:0000269|PubMed:12665569, ECO:0000269|PubMed:9632797"; MUTAGEN 1106; /note="Y->F: Reduced levels of autophosphorylation."; /evidence="ECO:0000269|PubMed:12665569
uniprot
proteins
post_translational_modification
PTM: Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2). {ECO:0000250}.; PTM: 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-990 in the kinase activation loop is phosphorylated first, followed by autophosphorylation at Tyr-1106 and at additional tyrosine residues. ANGPT1-induced phosphorylation is impaired during hypoxia, due to increased expression of ANGPT2 (By similarity). Phosphorylation is important for interaction with GRB14, PIK3R1 and PTPN11. Phosphorylation at Tyr-1100 is important for interaction with GRB2 and GRB7. Phosphorylation at Tyr-1106 is important for interaction with DOK2 and for coupling to downstream signal transduction pathways in endothelial cells. Dephosphorylated by PTPRB. {ECO:0000250, ECO:0000269|PubMed:10557082, ECO:0000269|PubMed:12665569}.; PTM: Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation (By similarity). {ECO:0000250}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tie subfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10521483
uniprot
proteins
pubmed
10557082
uniprot
proteins
pubmed
11375937
uniprot
proteins
pubmed
12427764
uniprot
proteins
pubmed
12665569
uniprot
proteins
pubmed
1282811
uniprot
proteins
pubmed
15284220
uniprot
proteins
pubmed
1630810
uniprot
proteins
pubmed
19451274
uniprot
proteins
pubmed
20973951
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
27270174
uniprot
proteins
pubmed
28179430
uniprot
proteins
pubmed
7596437
uniprot
proteins
pubmed
7958865
uniprot
proteins
pubmed
8187650
uniprot
proteins
pubmed
8217221
uniprot
proteins
pubmed
8386827
uniprot
proteins
pubmed
8395828
uniprot
proteins
pubmed
8415706
uniprot
proteins
pubmed
9632797
uniprot
proteins
sequence_length
1122
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Cell junction {ECO:0000250}. Cell junction, focal adhesion {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Secreted {ECO:0000250}. 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 (By similarity). {ECO:0000250}.
uniprot
proteins
transmembrane_region
TRANSMEM 747..767; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins