|TIE2_HUMAN » Angiopoietin-1 receptor » 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;|
|Hydrophobic Thickness||38.0 ± 2.0 Å|
|Tilt Angle||0 ± 0°|
|Links||UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome|
|TM Segments||746-772 (743-775)|
HIF-1 signaling pathway (KEGG)
PI3K-Akt signaling pathway (KEGG)
Rheumatoid arthritis (KEGG)
|PDB||2gy5 (23-445), 4x3j (802-1122), 2wqb (802-1124), 3l8p (808-1124), 2p4i (808-1124), 2osc (808-1124), 2oo8 (808-1124), 1fvr (808-1124), 3bea (917-935), 4k0v (A=23-542), 2gy7 (B=23-445)|
PTPRK, Complex: PTPRK:TIE2
PTPRO, Complex: TIE2:PTPRO
|UniProt annotation for TIE2_HUMAN » Angiopoietin-1 receptor|
|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 [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. 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. SUBUNIT: Homodimer. Heterodimer with TIE1. Interacts with ANGPT1, ANGPT2 and ANGPT4. At cell-cell contacts in quiescent cells, forms a signaling complex composed of ANGPT1 plus TEK molecules from two adjoining cells. In the absence of endothelial cell-cell contacts, interaction with ANGPT1 mediates contacts with the extracellular matrix. Interacts with PTPRB; this promotes endothelial cell-cell adhesion. Interacts with DOK2, GRB2, GRB7, GRB14, PIK3R1 and PTPN11/SHP2. Colocalizes with DOK2 at contacts with the extracellular matrix in migrating cells. Interacts (tyrosine phosphorylated) with TNIP2. Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain). TISSUE SPECIFICITY: Detected in umbilical vein endothelial cells. Proteolytic processing gives rise to a soluble extracellular domain that is detected in blood plasma (at protein level). Predominantly expressed in endothelial cells and their progenitors, the angioblasts. Has been directly found in placenta and lung, with a lower level in umbilical vein endothelial cells, brain and kidney. DOMAIN: The soluble extracellular domain is functionally active in angiopoietin binding and can modulate the activity of the membrane-bound form by competing for angiopoietins. DISEASE: Dominantly inherited venous malformations (VMCM) OMIM: An error of vascular morphogenesis characterized by dilated, serpiginous channels. disease is caused by mutations affecting the gene represented in this entry. DISEASE: Note=May play a role in a range of diseases with a vascular component, including neovascularization of tumors, psoriasis and inflammation.|
|UniProt features for TIE2_HUMAN » Angiopoietin-1 receptor|
SIGNAL 1 22 |
CHAIN 23 1124 Angiopoietin-1 receptor.
DOMAIN 44 123 Ig-like C2-type 1.
DOMAIN 210 252 EGF-like 1.
DOMAIN 254 299 EGF-like 2.
DOMAIN 301 341 EGF-like 3.
DOMAIN 350 440 Ig-like C2-type 2.
DOMAIN 445 537 Fibronectin type-III 1.
DOMAIN 544 633 Fibronectin type-III 2.
DOMAIN 639 730 Fibronectin type-III 3.
DOMAIN 824 1096 Protein kinase.
ACT_SITE 964 964 Proton acceptor (Probable).
DISULFID 44 102
DISULFID 211 220
DISULFID 224 233
DISULFID 227 240
DISULFID 242 251
DISULFID 255 264
DISULFID 268 274
DISULFID 280 287
DISULFID 289 298
DISULFID 302 311
DISULFID 315 323
DISULFID 317 329
DISULFID 331 340
DISULFID 370 424
|Amino Acid Sequence for TIE2_HUMAN » Angiopoietin-1 receptor|
|MDSLASLVLC GVSLLLSGTV EGAMDLILIN SLPLVSDAET SLTCIASGWR PHEPITIGRD FEALMNQHQD PLEVTQDVTR EWAKKVVWKR EKASKINGAY FCEGRVRGEA IRIRTMKMRQ QASFLPATLT MTVDKGDNVN ISFKKVLIKE EDAVIYKNGS FIHSVPRHEV PDILEVHLPH AQPQDAGVYS ARYIGGNLFT SAFTRLIVRR CEAQKWGPEC NHLCTACMNN GVCHEDTGEC ICPPGFMGRT CEKACELHTF GRTCKERCSG QEGCKSYVFC LPDPYGCSCA TGWKGLQCNE ACHPGFYGPD CKLRCSCNNG EMCDRFQGCL CSPGWQGLQC EREGIQRMTP KIVDLPDHIE VNSGKFNPIC KASGWPLPTN EEMTLVKPDG TVLHPKDFNH TDHFSVAIFT IHRILPPDSG VWVCSVNTVA GMVEKPFNIS VKVLPKPLNA PNVIDTGHNF AVINISSEPY FGDGPIKSKK LLYKPVNHYE AWQHIQVTNE IVTLNYLEPR TEYELCVQLV RRGEGGEGHP GPVRRFTTAS IGLPPPRGLN LLPKSQTTLN LTWQPIFPSS EDDFYVEVER RSVQKSDQQN IKVPGNLTSV LLNNLHPREQ YVVRARVNTK AQGEWSEDLT AWTLSDILPP QPENIKISNI THSSAVISWT ILDGYSISSI TIRYKVQGKN EDQHVDVKIK NATITQYQLK GLEPETAYQV DIFAENNIGS SNPAFSHELV TLPESQAPAD LGGGKMLLIA ILGSAGMTCL TVLLAFLIIL QLKRANVQRR MAQAFQNVRE EPAVQFNSGT LALNRKVKNN PDPTIYPVLD WNDIKFQDVI GEGNFGQVLK ARIKKDGLRM DAAIKRMKEY ASKDDHRDFA GELEVLCKLG HHPNIINLLG ACEHRGYLYL AIEYAPHGNL LDFLRKSRVL ETDPAFAIAN STASTLSSQQ LLHFAADVAR GMDYLSQKQF IHRDLAARNI LVGENYVAKI ADFGLSRGQE VYVKKTMGRL PVRWMAIESL NYSVYTTNSD VWSYGVLLWE IVSLGGTPYC GMTCAELYEK LPQGYRLEKP LNCDDEVYDL MRQCWREKPY ERPSFAQILV SLNRMLEERK TYVNTTLYEK FTYAGIDCSA EEAA|