Angiopoietin-1 receptor

UniProt data

UniProt name: TIE2_HUMAN (Q02763)

Gene name: TEK; Synonyms=TIE2, VMCM, VMCM1

Organism: Homo sapiens (Human).

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. {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}.

Subcellular location: Cell membrane; Single-pass type I membrane protein. Cell junction. Cell junction, focal adhesion. Cytoplasm, cytoskeleton. Secreted. 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.

Transmembrane domains:

  1. 749-769, 21 AA, Helical. {ECO:0000255}.

Sequence: 1124 AA

10 20 30 40 50 60 MDSLASLVLC GVSLLLSGTV EGAMDLILIN SLPLVSDAET SLTCIASGWR PHEPITIGRD 70 80 90 100 110 120 FEALMNQHQD PLEVTQDVTR EWAKKVVWKR EKASKINGAY FCEGRVRGEA IRIRTMKMRQ 130 140 150 160 170 180 QASFLPATLT MTVDKGDNVN ISFKKVLIKE EDAVIYKNGS FIHSVPRHEV PDILEVHLPH 190 200 210 220 230 240 AQPQDAGVYS ARYIGGNLFT SAFTRLIVRR CEAQKWGPEC NHLCTACMNN GVCHEDTGEC 250 260 270 280 290 300 ICPPGFMGRT CEKACELHTF GRTCKERCSG QEGCKSYVFC LPDPYGCSCA TGWKGLQCNE 310 320 330 340 350 360 ACHPGFYGPD CKLRCSCNNG EMCDRFQGCL CSPGWQGLQC EREGIQRMTP KIVDLPDHIE 370 380 390 400 410 420 VNSGKFNPIC KASGWPLPTN EEMTLVKPDG TVLHPKDFNH TDHFSVAIFT IHRILPPDSG 430 440 450 460 470 480 VWVCSVNTVA GMVEKPFNIS VKVLPKPLNA PNVIDTGHNF AVINISSEPY FGDGPIKSKK 490 500 510 520 530 540 LLYKPVNHYE AWQHIQVTNE IVTLNYLEPR TEYELCVQLV RRGEGGEGHP GPVRRFTTAS 550 560 570 580 590 600 IGLPPPRGLN LLPKSQTTLN LTWQPIFPSS EDDFYVEVER RSVQKSDQQN IKVPGNLTSV 610 620 630 640 650 660 LLNNLHPREQ YVVRARVNTK AQGEWSEDLT AWTLSDILPP QPENIKISNI THSSAVISWT 670 680 690 700 710 720 ILDGYSISSI TIRYKVQGKN EDQHVDVKIK NATITQYQLK GLEPETAYQV DIFAENNIGS 730 740 750 760 770 780 SNPAFSHELV TLPESQAPAD LGGGKMLLIA ILGSAGMTCL TVLLAFLIIL QLKRANVQRR 790 800 810 820 830 840 MAQAFQNVRE EPAVQFNSGT LALNRKVKNN PDPTIYPVLD WNDIKFQDVI GEGNFGQVLK 850 860 870 880 890 900 ARIKKDGLRM DAAIKRMKEY ASKDDHRDFA GELEVLCKLG HHPNIINLLG ACEHRGYLYL 910 920 930 940 950 960 AIEYAPHGNL LDFLRKSRVL ETDPAFAIAN STASTLSSQQ LLHFAADVAR GMDYLSQKQF 970 980 990 1000 1010 1020 IHRDLAARNI LVGENYVAKI ADFGLSRGQE VYVKKTMGRL PVRWMAIESL NYSVYTTNSD 1030 1040 1050 1060 1070 1080 VWSYGVLLWE IVSLGGTPYC GMTCAELYEK LPQGYRLEKP LNCDDEVYDL MRQCWREKPY 1090 1100 1110 1120 ERPSFAQILV SLNRMLEERK TYVNTTLYEK FTYAGIDCSA EEAA

CATM prediction

The sequence of TIE2_HUMAN returned 1 potential models

The positions at the dimer's interface are highlighted in yellow. The position at the crossing point is highlighted in orange.

# Sequence and interface d θ Z' ω' Score
      750       760       770
    |    +    |    +    |  		 (Å) (°) (Å) (°)  
Model 1 MLLIAILGSAGMTCLTVLLAFLIILQL 7.1 -53.2° 2.0 44.8 -29.5

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MODEL 1 DETAILS

Precited structure:


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Download model 1 structure: PDB, PyMOL session

List of hydrogen bonds:

Donor Acceptor Distance
B, 750, ALA, HA A, 749, ILE, O 3.36Å
B, 753, GLY, HA1 A, 750, ALA, O 3.01Å
A, 750, ALA, HA B, 749, ILE, O 3.36Å
A, 753, GLY, HA1 B, 750, ALA, O 3.01Å