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
- UniProtKB Entry
- Q02763Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- 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
- Functionsgrowth factor binding / identical protein binding / signaling receptor activityProcessescell surface receptor protein tyrosine kinase signaling pathway / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of Rac protein signal transduction / positive regulation of Rho protein signal transduction / response to peptide hormoneComponentscentriolar satellite / cytoplasm / receptor complex
- General 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
- Specific Function
- ATP binding
- Pfam Domain Function
- Signal Regions
- 1-22
- 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
- 9p21.2
- External Identifiers
Resource Link UniProtKB ID Q02763 UniProtKB Entry Name TIE2_HUMAN GenBank Gene ID L06139 GeneCard ID TEK GenAtlas ID TEK HGNC ID HGNC:11724 PDB ID(s) 1FVR, 2GY5, 2GY7, 2OO8, 2OSC, 2P4I, 2WQB, 3BEA, 3L8P, 4K0V, 4X3J, 5MYA, 5MYB, 5UTK, 6MWE, 7E72 KEGG ID hsa:7010 IUPHAR/Guide To Pharmacology ID 1842 NCBI Gene ID 7010 - General References
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Associated Data
- Bio-Entities
Bio-Entity Type Angiopoietin-1 receptor (Humans) protein primary- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details N-{4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDE experimental unknown target Details Vandetanib approved unknown target inhibitor Details Regorafenib approved yes target inhibitor Details Ponatinib approved, investigational unknown target inhibitor Details Ampicillin approved, vet_approved unknown target Details Fostamatinib approved, investigational unknown target inhibitor Details Ripretinib approved yes target inhibitor Details Tivozanib approved, investigational unknown target Details Pexmetinib investigational yes target modulator Details Altiratinib investigational yes target inhibitor Details Rebastinib investigational yes target inhibitor Details Razuprotafib investigational yes target activator Details