TEK
entrez
7010
canonical
uniprot
Q02763
canonical
ensembl
ENSG00000120156
resolver
ensp
ENSP00000369375
resolver
ensp
ENSP00000383977
resolver
ensp
ENSP00000430686
resolver
ensp
ENSP00000526771
resolver
ensp
ENSP00000526772
resolver
genesymbol
TEK
resolver
genesymbol_syn
TIE2
resolver
genesymbol_syn
VMCM
resolver
genesymbol_syn
VMCM1
resolver
hgnc
HGNC:11724
resolver
uniprot
A8K6W0
resolver
uniprot
B4DH20
resolver
uniprot
B4DHD3
resolver
uniprot
D3DRK5
resolver
uniprot
E7EWI2
resolver
uniprot
Q59HG2
resolver
uniprot
Q5TCU2
resolver
uniprot
Q8IV34
resolver
uniprot_entry
Q59HG2_HUMAN
resolver
uniprot_entry
TIE2_HUMAN
resolver
uniprot_sec
A8K6W0
resolver
uniprot_sec
B4DH20
resolver
uniprot_sec
B4DHD3
resolver
uniprot_sec
D3DRK5
resolver
uniprot_sec
E7EWI2
resolver
uniprot_sec
Q5TCU2
resolver
uniprot_sec
Q8IV34
resolver
activity_regulation
ACTIVITY 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. {ECO:0000269|PubMed:11080633, ECO:0000269|PubMed:11513602, ECO:0000269|PubMed:17253678, ECO:0000269|PubMed:17350837, ECO:0000269|PubMed:19854647, ECO:0000269|PubMed:20651738}.
uniprot
proteins
amino_acid_sequence
MDSLASLVLCGVSLLLSGTVEGAMDLILINSLPLVSDAETSLTCIASGWRPHEPITIGRDFEALMNQHQDPLEVTQDVTREWAKKVVWKREKASKINGAYFCEGRVRGEAIRIRTMKMRQQASFLPATLTMTVDKGDNVNISFKKVLIKEEDAVIYKNGSFIHSVPRHEVPDILEVHLPHAQPQDAGVYSARYIGGNLFTSAFTRLIVRRCEAQKWGPECNHLCTACMNNGVCHEDTGECICPPGFMGRTCEKACELHTFGRTCKERCSGQEGCKSYVFCLPDPYGCSCATGWKGLQCNEACHPGFYGPDCKLRCSCNNGEMCDRFQGCLCSPGWQGLQCEREGIQRMTPKIVDLPDHIEVNSGKFNPICKASGWPLPTNEEMTLVKPDGTVLHPKDFNHTDHFSVAIFTIHRILPPDSGVWVCSVNTVAGMVEKPFNISVKVLPKPLNAPNVIDTGHNFAVINISSEPYFGDGPIKSKKLLYKPVNHYEAWQHIQVTNEIVTLNYLEPRTEYELCVQLVRRGEGGEGHPGPVRRFTTASIGLPPPRGLNLLPKSQTTLNLTWQPIFPSSEDDFYVEVERRSVQKSDQQNIKVPGNLTSVLLNNLHPREQYVVRARVNTKAQGEWSEDLTAWTLSDILPPQPENIKISNITHSSAVISWTILDGYSISSITIRYKVQGKNEDQHVDVKIKNATITQYQLKGLEPETAYQVDIFAENNIGSSNPAFSHELVTLPESQAPADLGGGKMLLIAILGSAGMTCLTVLLAFLIILQLKRANVQRRMAQAFQNVREEPAVQFNSGTLALNRKVKNNPDPTIYPVLDWNDIKFQDVIGEGNFGQVLKARIKKDGLRMDAAIKRMKEYASKDDHRDFAGELEVLCKLGHHPNIINLLGACEHRGYLYLAIEYAPHGNLLDFLRKSRVLETDPAFAIANSTASTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRGQEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYDLMRQCWREKPYERPSFAQILVSLNRMLEERKTYVNTTLYEKFTYAGIDCSAEEAA
uniprot
proteins
disease_involvement
DISEASE: Dominantly inherited venous malformations (VMCM) [MIM:600195]: An error of vascular morphogenesis characterized by dilated, serpiginous channels. {ECO:0000269|PubMed:10369874, ECO:0000269|PubMed:19079259, ECO:0000269|PubMed:19888299, ECO:0000269|PubMed:8980225}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=Somatic mutations of TEK are associated with solitary and multiple sporadic venous malformations. {ECO:0000269|PubMed:19079259}.; DISEASE: Note=May play a role in a range of diseases with a vascular component, including neovascularization of tumors, psoriasis and inflammation.; DISEASE: Glaucoma 3, primary congenital, E (GLC3E) [MIM:617272]: An autosomal dominant form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor. {ECO:0000269|PubMed:27270174}. Note=The disease is caused by variants affecting the gene represented in this entry.
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 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. {ECO:0000269|PubMed:12816861, ECO:0000269|PubMed:14665640, ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:15851516, ECO:0000269|PubMed:18366015, ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120, ECO:0000269|PubMed:19223473, ECO:0000269|PubMed:20651738, ECO:0000269|PubMed:9204896}.
uniprot
proteins
mass_dalton
125830
uniprot
proteins
mutagenesis
MUTAGEN 224; /note="C->S: Reduces protein abundance."; /evidence="ECO:0000269|PubMed:27270174"; MUTAGEN 855; /note="K->R: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:12609966, ECO:0000269|PubMed:15851516"; MUTAGEN 1102; /note="Y->F: Abolishes interaction with SHC1."; /evidence="ECO:0000269|PubMed:14665640
uniprot
proteins
post_translational_modification
PTM: Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2). {ECO:0000269|PubMed:11806244}.; 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-992 in the kinase activation loop is phosphorylated first, followed by autophosphorylation at Tyr-1108 and at additional tyrosine residues. ANGPT1-induced phosphorylation is impaired during hypoxia, due to increased expression of ANGPT2. Phosphorylation is important for interaction with GRB14, PIK3R1 and PTPN11. Phosphorylation at Tyr-1102 is important for interaction with SHC1, GRB2 and GRB7. Phosphorylation at Tyr-1108 is important for interaction with DOK2 and for coupling to downstream signal transduction pathways in endothelial cells. Dephosphorylated by PTPRB. {ECO:0000269|PubMed:11513602, ECO:0000269|PubMed:14665640}.; PTM: Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation. {ECO:0000269|PubMed:19689429}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tie subfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10369874
uniprot
proteins
pubmed
11080633
uniprot
proteins
pubmed
11513602
uniprot
proteins
pubmed
11806244
uniprot
proteins
pubmed
12609966
uniprot
proteins
pubmed
12816861
uniprot
proteins
pubmed
14665640
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15284220
uniprot
proteins
pubmed
15340161
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15851516
uniprot
proteins
pubmed
16732286
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17253678
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17350837
uniprot
proteins
pubmed
18366015
uniprot
proteins
pubmed
18425119
uniprot
proteins
pubmed
18425120
uniprot
proteins
pubmed
19079259
uniprot
proteins
pubmed
19116766
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19223473
uniprot
proteins
pubmed
19234476
uniprot
proteins
pubmed
19293632
uniprot
proteins
pubmed
19451274
uniprot
proteins
pubmed
19689429
uniprot
proteins
pubmed
19854647
uniprot
proteins
pubmed
19888299
uniprot
proteins
pubmed
20054809
uniprot
proteins
pubmed
20651738
uniprot
proteins
pubmed
27270174
uniprot
proteins
pubmed
32908006
uniprot
proteins
pubmed
8382358
uniprot
proteins
pubmed
8980225
uniprot
proteins
pubmed
9204896
uniprot
proteins
sequence_length
1124
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120, ECO:0000269|PubMed:19079259, ECO:0000269|PubMed:27270174}; Single-pass type I membrane protein. Cell junction {ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120, ECO:0000269|PubMed:27270174}. Cell junction, focal adhesion {ECO:0000305|PubMed:19293632}. Cytoplasm, cytoskeleton. Secreted {ECO:0000269|PubMed:11806244}. Note=Recruited to cell-cell contacts in quiescent endothelial cells (PubMed:18425119, PubMed:18425120). 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 (PubMed:11806244). {ECO:0000269|PubMed:11806244, ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120}.
uniprot
proteins
transmembrane_region
TRANSMEM 749..769; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins