Angiopoietin-1 receptor

Details

Name
Angiopoietin-1 receptor
Synonyms
  • 2.7.10.1
  • Endothelial tyrosine kinase
  • hTIE2
  • p140 TEK
  • TIE2
  • 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
  • VMCM
  • VMCM1
Gene Name
TEK
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037228|Angiopoietin-1 receptor
MDSLASLVLCGVSLLLSGTVEGAMDLILINSLPLVSDAETSLTCIASGWRPHEPITIGRD
FEALMNQHQDPLEVTQDVTREWAKKVVWKREKASKINGAYFCEGRVRGEAIRIRTMKMRQ
QASFLPATLTMTVDKGDNVNISFKKVLIKEEDAVIYKNGSFIHSVPRHEVPDILEVHLPH
AQPQDAGVYSARYIGGNLFTSAFTRLIVRRCEAQKWGPECNHLCTACMNNGVCHEDTGEC
ICPPGFMGRTCEKACELHTFGRTCKERCSGQEGCKSYVFCLPDPYGCSCATGWKGLQCNE
ACHPGFYGPDCKLRCSCNNGEMCDRFQGCLCSPGWQGLQCEREGIQRMTPKIVDLPDHIE
VNSGKFNPICKASGWPLPTNEEMTLVKPDGTVLHPKDFNHTDHFSVAIFTIHRILPPDSG
VWVCSVNTVAGMVEKPFNISVKVLPKPLNAPNVIDTGHNFAVINISSEPYFGDGPIKSKK
LLYKPVNHYEAWQHIQVTNEIVTLNYLEPRTEYELCVQLVRRGEGGEGHPGPVRRFTTAS
IGLPPPRGLNLLPKSQTTLNLTWQPIFPSSEDDFYVEVERRSVQKSDQQNIKVPGNLTSV
LLNNLHPREQYVVRARVNTKAQGEWSEDLTAWTLSDILPPQPENIKISNITHSSAVISWT
ILDGYSISSITIRYKVQGKNEDQHVDVKIKNATITQYQLKGLEPETAYQVDIFAENNIGS
SNPAFSHELVTLPESQAPADLGGGKMLLIAILGSAGMTCLTVLLAFLIILQLKRANVQRR
MAQAFQNVREEPAVQFNSGTLALNRKVKNNPDPTIYPVLDWNDIKFQDVIGEGNFGQVLK
ARIKKDGLRMDAAIKRMKEYASKDDHRDFAGELEVLCKLGHHPNIINLLGACEHRGYLYL
AIEYAPHGNLLDFLRKSRVLETDPAFAIANSTASTLSSQQLLHFAADVARGMDYLSQKQF
IHRDLAARNILVGENYVAKIADFGLSRGQEVYVKKTMGRLPVRWMAIESLNYSVYTTNSD
VWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYDLMRQCWREKPY
ERPSFAQILVSLNRMLEERKTYVNTTLYEKFTYAGIDCSAEEAA
Number of residues
1124
Molecular Weight
125829.005
Theoretical pI
6.88
GO Classification
Functions
ATP binding / protein kinase activity / protein tyrosine kinase activity / receptor activity / transmembrane receptor protein tyrosine kinase activity
Processes
activation of MAPKK activity / angiogenesis / axon guidance / blood coagulation / cell-cell signaling / cell-matrix adhesion / 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 cytokine secretion involved in immune response / 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 peptidyl-serine phosphorylation / positive regulation of phosphatidylinositol 3-kinase activity / positive regulation of phosphatidylinositol 3-kinase signaling / positive regulation of protein import into nucleus / 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 NIK/NF-kappaB signaling / regulation of vascular permeability / response to cAMP / response to estrogen / response to hypoxia / signal transduction / single organismal cell-cell adhesion / 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
Components
apical plasma membrane / basal plasma membrane / basolateral plasma membrane / cell surface / cell-cell junction / cytoskeleton / extracellular region / focal adhesion / integral component of plasma membrane / membrane raft / microvillus / perinuclear region of cytoplasm / plasma membrane
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
749-769
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0017082|Angiopoietin-1 receptor (TEK)
ATGGACTCTTTAGCCAGCTTAGTTCTCTGTGGAGTCAGCTTGCTCCTTTCTGGAACTGTG
GAAGGTGCCATGGACTTGATCTTGATCAATTCCCTACCTCTTGTATCTGATGCTGAAACA
TCTCTCACCTGCATTGCCTCTGGGTGGCGCCCCCATGAGCCCATCACCATAGGAAGGGAC
TTTGAAGCCTTAATGAACCAGCACCAGGATCCGCTGGAAGTTACTCAAGATGTGACCAGA
GAATGGGCTAAAAAAGTTGTTTGGAAGAGAGAAAAGGCTAGTAAGATCAATGGTGCTTAT
TTCTGTGAAGGGCGAGTTCGAGGAGAGGCAATCAGGATACGAACCATGAAGATGCGTCAA
CAAGCTTCCTTCCTACCAGCTACTTTAACTATGACTGTGGACAAGGGAGATAACGTGAAC
ATATCTTTCAAAAAGGTATTGATTAAAGAAGAAGATGCAGTGATTTACAAAAATGGTTCC
TTCATCCATTCAGTGCCCCGGCATGAAGTACCTGATATTCTAGAAGTACACCTGCCTCAT
GCTCAGCCCCAGGATGCTGGAGTGTACTCGGCCAGGTATATAGGAGGAAACCTCTTCACC
TCGGCCTTCACCAGGCTGATAGTCCGGAGATGTGAAGCCCAGAAGTGGGGACCTGAATGC
AACCATCTCTGTACTGCTTGTATGAACAATGGTGTCTGCCATGAAGATACTGGAGAATGC
ATTTGCCCTCCTGGGTTTATGGGAAGGACGTGTGAGAAGGCTTGTGAACTGCACACGTTT
GGCAGAACTTGTAAAGAAAGGTGCAGTGGACAAGAGGGATGCAAGTCTTATGTGTTCTGT
CTCCCTGACCCCTATGGGTGTTCCTGTGCCACAGGCTGGAAGGGTCTGCAGTGCAATGAA
GCATGCCACCCTGGTTTTTACGGGCCAGATTGTAAGCTTAGGTGCAGCTGCAACAATGGG
GAGATGTGTGATCGCTTCCAAGGATGTCTCTGCTCTCCAGGATGGCAGGGGCTCCAGTGT
GAGAGAGAAGGCATACCGAGGATGACCCCAAAGATAGTGGATTTGCCAGATCATATAGAA
GTAAACAGTGGTAAATTTAATCCCATTTGCAAAGCTTCTGGCTGGCCGCTACCTACTAAT
GAAGAAATGACCCTGGTGAAGCCGGATGGGACAGTGCTCCATCCAAAAGACTTTAACCAT
ACGGATCATTTCTCAGTAGCCATATTCACCATCCACCGGATCCTCCCCCCTGACTCAGGA
GTTTGGGTCTGCAGTGTGAACACAGTGGCTGGGATGGTGGAAAAGCCCTTCAACATTTCT
GTTAAAGTTCTTCCAAAGCCCCTGAATGCCCCAAACGTGATTGACACTGGACATAACTTT
GCTGTCATCAACATCAGCTCTGAGCCTTACTTTGGGGATGGACCAATCAAATCCAAGAAG
CTTCTATACAAACCCGTTAATCACTATGAGGCTTGGCAACATATTCAAGTGACAAATGAG
ATTGTTACACTCAACTATTTGGAACCTCGGACAGAATATGAACTCTGTGTGCAACTGGTC
CGTCGTGGAGAGGGTGGGGAAGGGCATCCTGGACCTGTGAGACGCTTCACAACAGCTTCT
ATCGGACTCCCTCCTCCAAGAGGTCTAAATCTCCTGCCTAAAAGTCAGACCACTCTAAAT
TTGACCTGGCAACCAATATTTCCAAGCTCGGAAGATGACTTTTATGTTGAAGTGGAGAGA
AGGTCTGTGCAAAAAAGTGATCAGCAGAATATTAAAGTTCCAGGCAACTTGACTTCGGTG
CTACTTAACAACTTACATCCCAGGGAGCAGTACGTGGTCCGAGCTAGAGTCAACACCAAG
GCCCAGGGGGAATGGAGTGAAGATCTCACTGCTTGGACCCTTAGTGACATTCTTCCTCCT
CAACCAGAAAACATCAAGATTTCCAACATTACACACTCCTCAGCTGTGATTTCTTGGACA
ATATTGGATGGCTATTCTATTTCTTCTATTACTATCCGTTACAAGGTTCAAGGCAAGAAT
GAAGACCAGCACGTTGATGTGAAGATAAAGAATGCCACCATCACTCAGTATCAGCTCAAG
GGCCTAGAGCCTGAAACAGCATACCAGGTGGACATTTTTGCAGAGAACAACATAGGGTCA
AGCAACCCAGCCTTTTCTCATGAACTGGTGACCCTCCCAGAATCTCAAGCACCAGCGGAC
CTCGGAGGGGGGAAGATGCTGCTTATAGCCATCCTTGGCTCTGCTGGAATGACCTGCCTG
ACTGTGCTGTTGGCCTTTCTGATCATATTGCAATTGAAGAGGGCAAATGTGCAAAGGAGA
ATGGCCCAAGCCTTCCAAAACGTGAGGGAAGAACCAGCTGTGCAGTTCAACTCAGGGACT
CTGGCCCTAAACAGGAAGGTCAAAAACAACCCAGATCCTACAATTTATCCAGTGCTTGAC
TGGAATGACATCAAATTTCAAGATGTGATTGGGGAGGGCAATTTTGGCCAAGTTCTTAAG
GCGCGCATCAAGAAGGATGGGTTACGGATGGATGCTGCCATCAAAAGAATGAAAGAATAT
GCCTCCAAAGATGATCACAGGGACTTTGCAGGAGAACTGGAAGTTCTTTGTAAACTTGGA
CACCATCCAAACATCATCAATCTCTTAGGAGCATGTGAACATCGAGGCTACTTGTACCTG
GCCATTGAGTACGCGCCCCATGGAAACCTTCTGGACTTCCTTCGCAAGAGCCGTGTGCTG
GAGACGGACCCAGCATTTGCCATTGCCAATAGCACCGCGTCCACACTGTCCTCCCAGCAG
CTCCTTCACTTCGCTGCCGACGTGGCCCGGGGCATGGACTACTTGAGCCAAAAACAGTTT
ATCCACAGGGATCTGGCTGCCAGAAACATTTTAGTTGGTGAAAACTATGTGGCAAAAATA
GCAGATTTTGGATTGTCCCGAGGTCAAGAGGTGTATGTGAAAAAGACAATGGGAAGGCTC
CCAGTGCGCTGGATGGCCATCGAGTCACTGAATTACAGTGTGTACACAACCAACAGTGAT
GTATGGTCCTATGGTGTGTTACTATGGGAGATTGTTAGCTTAGGAGGCACACCCTACTGC
GGGATGACTTGTGCAGAACTCTACGAGAAGCTGCCCCAGGGCTACAGACTGGAGAAGCCC
CTGAACTGTGATGATGAGGTGTATGATCTAATGAGACAATGCTGGCGGGAGAAGCCTTAT
GAGAGGCCATCATTTGCCCAGATATTGGTGTCCTTAAACAGAATGTTAGAGGAGCGAAAG
ACCTACGTGAATACCACGCTTTATGAGAAGTTTACTTATGCAGGAATTGACTGTTCTGCT
GAAGAAGCGGCCTAG
Chromosome Location
9
Locus
9p21
External Identifiers
ResourceLink
UniProtKB IDQ02763
UniProtKB Entry NameTIE2_HUMAN
GenBank Gene IDL06139
GenAtlas IDTEK
HGNC IDHGNC:11724
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB08221N-{4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDEexperimentalunknownDetails
DB05294VandetanibapprovedunknowninhibitorDetails
DB08896RegorafenibapprovedyesinhibitorDetails
DB08901Ponatinibapproved, investigationalunknowninhibitorDetails
DB00415Ampicillinapproved, vet_approvedunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails