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Protein

Angiopoietin-1 receptor

Gene

TEK

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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 (By similarity).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-993 on the kinase activation loop.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei856ATPPROSITE-ProRule annotation1
Active sitei965Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi831 – 839ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 908
ReactomeiR-BTA-210993 Tie2 Signaling
R-BTA-5673001 RAF/MAP kinase cascade

Names & Taxonomyi

Protein namesi
Recommended name:
Angiopoietin-1 receptor (EC:2.7.10.1)
Alternative name(s):
Endothelial tyrosine kinase
Tyrosine kinase with Ig and EGF homology domains-2
Tyrosine-protein kinase receptor TIE-2
CD_antigen: CD202b
Gene namesi
Name:TEK
Synonyms:TIE-2, TIE2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 8

Organism-specific databases

VGNCiVGNC:35735 TEK

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 748ExtracellularSequence analysisAdd BLAST726
Transmembranei749 – 769HelicalSequence analysisAdd BLAST21
Topological domaini770 – 1125CytoplasmicSequence analysisAdd BLAST356

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22By similarityAdd BLAST22
ChainiPRO_000002447323 – 1125Angiopoietin-1 receptorAdd BLAST1103

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi44 ↔ 102By similarity
Glycosylationi158N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi211 ↔ 220By similarity
Disulfide bondi224 ↔ 233By similarity
Disulfide bondi227 ↔ 240By similarity
Disulfide bondi242 ↔ 251By similarity
Disulfide bondi255 ↔ 264By similarity
Disulfide bondi268 ↔ 274By similarity
Disulfide bondi280 ↔ 287By similarity
Disulfide bondi289 ↔ 298By similarity
Disulfide bondi302 ↔ 311By similarity
Disulfide bondi315 ↔ 323By similarity
Disulfide bondi317 ↔ 329By similarity
Disulfide bondi331 ↔ 340By similarity
Disulfide bondi370 ↔ 424By similarity
Modified residuei861Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei993Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1103Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1109Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2).By similarity
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-993 in the kinase activation loop is phosphorylated first, followed by autophosphorylation at Tyr-1109 and at additional tyrosine residues. ANGPT1-induced phosphorylation is impaired during hypoxia, due to increased expression of ANGPT2 (By similarity). Phosphorylation is important for interaction with GRB14, PIK3R1 and PTPN11. Phosphorylation at Tyr-1103 is important for interaction with GRB2 and GRB7. Phosphorylation at Tyr-1109 is important for interaction with DOK2 and for coupling to downstream signal transduction pathways in endothelial cells. Dephosphorylated by PTPRB (By similarity).By similarity
Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ06807
PeptideAtlasiQ06807
PRIDEiQ06807

Expressioni

Tissue specificityi

Specifically expressed in developing vascular endothelial cells.

Gene expression databases

BgeeiENSBTAG00000020148

Interactioni

Subunit structurei

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 (tyrosine phosphorylated) with TNIP2. Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain) (By similarity). 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 (By similarity).By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000026836

Structurei

3D structure databases

ProteinModelPortaliQ06807
SMRiQ06807
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 123Ig-like C2-type 1Add BLAST80
Domaini210 – 252EGF-like 1PROSITE-ProRule annotationAdd BLAST43
Domaini254 – 299EGF-like 2PROSITE-ProRule annotationAdd BLAST46
Domaini301 – 341EGF-like 3PROSITE-ProRule annotationAdd BLAST41
Domaini350 – 440Ig-like C2-type 2Add BLAST91
Domaini447 – 541Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST95
Domaini545 – 637Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST93
Domaini642 – 735Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST94
Domaini825 – 1097Protein kinasePROSITE-ProRule annotationAdd BLAST273

Domaini

The soluble extracellular domain is functionally active in angiopoietin binding and can modulate the activity of the membrane-bound form by competing for angiopoietins.By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Tie subfamily.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00910000144091
HOGENOMiHOG000049232
HOVERGENiHBG007316
InParanoidiQ06807
KOiK05121
OMAiAIEYAPH
OrthoDBiEOG091G00RL
TreeFamiTF317568

Family and domain databases

CDDicd00063 FN3, 2 hits
Gene3Di2.60.40.10, 6 hits
InterProiView protein in InterPro
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR018941 Tyr_kin_Tie2_Ig-like_dom-1_N
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF00041 fn3, 3 hits
PF10430 Ig_Tie2_1, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00181 EGF, 2 hits
SM00060 FN3, 3 hits
SM00220 S_TKc, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit
SSF49265 SSF49265, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00022 EGF_1, 3 hits
PS01186 EGF_2, 2 hits
PS50026 EGF_3, 1 hit
PS50853 FN3, 3 hits
PS50835 IG_LIKE, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q06807-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDSLAGLVLC GVSLLLSATV DGAMDLILIN SLPLVSDAET SLTCIASGWR
60 70 80 90 100
PHEPITIGRD FEALMNQHQD PLEVTQDATR EWAKKVVWKR EKASKINGAY
110 120 130 140 150
FCEGRVRGQA IRIRTMKMRQ QASFLPATLT MTVDRGDNVN ISFKKVLIKE
160 170 180 190 200
EDAVIYKNGS FIHSVPRHEV PDILEVQVPH AQPQDAGVYS ARYIGGNLFT
210 220 230 240 250
SAFTRLIVRR CEAQKWGPEC NRICTACMNN GICHEDTGEC ICPPGFMGRT
260 270 280 290 300
CEKACEPHTF GRTCKERCSE PEGCKSFVFC LPDPYGCSCA TGWKGLQCNE
310 320 330 340 350
ACQPGYYGPD CKLRCSCTNG EKCDRFQGCL CSPGRQGLQC EKEGVPRMTP
360 370 380 390 400
KIEDLPDHIE VNSGKFNPIC KASGWPRPAN EEMTLVKPDG TVLRPKDFNH
410 420 430 440 450
TGHLSVATFT INRILPPDSG VWVCSVNTVS GMVEKPFNIS VKVLPKPLNA
460 470 480 490 500
PKVIDTGHNF AVINISSEPY FGDGPIKSKK LLYKPVNHYE AWRHIQVTNE
510 520 530 540 550
IVTLNYLEPR TEYELCVQLV RRGEGGEGHP GPVRRFTTAS IGLPPPRGLS
560 570 580 590 600
LLPKSQTTLN LTWQPIFPSS EDDFYVEVER RSVQMNSDQQ NIKVPGNLTS
610 620 630 640 650
VLLNNLHPRE QYIVRARVNT KAQGEWSEDL IAWTLSDIVP PQPENIKIFN
660 670 680 690 700
ITDSSAVISW TILDGYSISA IIIRYKVQGK NEDQHIDVKI KNATITQYQL
710 720 730 740 750
KGLEPQTVYQ VDIFAENNIG SSNPTSSHEL TTLSESQAPA DLGGRKMLLI
760 770 780 790 800
AILGSAGMTC LTVLLAFLIM LQLKRANVQR RMAQAFQNVR EEPAVQFNSG
810 820 830 840 850
TLALNRKAKN NPDPTIYPVL DWNDIKFQDV IGEGNFGQVL KARIKKDGLR
860 870 880 890 900
MDAAIKRMKE YASKDDHRDF AGELEVLCKL GHHPNIINLL GACEHRGYLY
910 920 930 940 950
LAIEYAPHGN LLDFLRKSRV LETDPAFAIA NSTASTLSSQ QLLHFAADVA
960 970 980 990 1000
RGMDYLSQKQ FIHRDLAARN ILVGENYVAK IADFGLSRGQ EVYVKKTMGR
1010 1020 1030 1040 1050
LPVRWMAIES LNYSVYTTNS DVWSYGVLLW EIVSLGGTPY CGMTCAELYE
1060 1070 1080 1090 1100
KLPQGYRLEK PLNCDDEVYD LMRQCWREKP YERPSFAQIL VSLNRMLEER
1110 1120
KTYVNTTLYE KFTYAGIDCS AEEAA
Length:1,125
Mass (Da):125,927
Last modified:February 1, 1995 - v1
Checksum:i015F1320AB853B7F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X71424 mRNA Translation: CAA50555.1
PIRiS57846
RefSeqiNP_776389.1, NM_173964.2
UniGeneiBt.4390

Genome annotation databases

EnsembliENSBTAT00000026836; ENSBTAP00000026836; ENSBTAG00000020148
GeneIDi280939
KEGGibta:280939

Similar proteinsi

Entry informationi

Entry nameiTIE2_BOVIN
AccessioniPrimary (citable) accession number: Q06807
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: March 28, 2018
This is version 162 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health