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Protein

Angiopoietin-1 receptor

Gene

TEK

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei856 – 8561ATPPROSITE-ProRule annotation
Active sitei965 – 9651Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi831 – 8399ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-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

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 748726ExtracellularSequence analysisAdd
BLAST
Transmembranei749 – 76921HelicalSequence analysisAdd
BLAST
Topological domaini770 – 1125356CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222By similarityAdd
BLAST
Chaini23 – 11251103Angiopoietin-1 receptorPRO_0000024473Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi44 ↔ 102By similarity
Glycosylationi158 – 1581N-linked (GlcNAc...)Sequence analysis
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 residuei861 – 8611Phosphotyrosine; by autocatalysisBy similarity
Modified residuei993 – 9931Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1103 – 11031Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1109 – 11091Phosphotyrosine; by autocatalysisBy similarity

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.

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. Positions 23-445, 814-1122.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 12380Ig-like C2-type 1Add
BLAST
Domaini210 – 25243EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini254 – 29946EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini301 – 34141EGF-like 3PROSITE-ProRule annotationAdd
BLAST
Domaini350 – 44091Ig-like C2-type 2Add
BLAST
Domaini447 – 54195Fibronectin type-III 1PROSITE-ProRule annotationAdd
BLAST
Domaini545 – 63793Fibronectin type-III 2PROSITE-ProRule annotationAdd
BLAST
Domaini642 – 73594Fibronectin type-III 3PROSITE-ProRule annotationAdd
BLAST
Domaini825 – 1097273Protein kinasePROSITE-ProRule annotationAdd
BLAST

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
Contains 3 EGF-like domains.PROSITE-ProRule annotation
Contains 3 fibronectin type-III domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

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

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00830000128295.
HOGENOMiHOG000049232.
HOVERGENiHBG007316.
InParanoidiQ06807.
KOiK05121.
OMAiCHEDTGE.
OrthoDBiEOG7966FR.
TreeFamiTF317568.

Family and domain databases

Gene3Di2.60.40.10. 6 hits.
InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR003961. FN3_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamiPF00041. fn3. 3 hits.
PF10430. Ig_Tie2_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00181. EGF. 2 hits.
SM00060. FN3. 3 hits.
SM00220. S_TKc. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF49265. SSF49265. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00022. 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.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ06807.
SMRiQ06807. Positions 23-445, 814-1122.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000026836.

Proteomic databases

PaxDbiQ06807.
PeptideAtlasiQ06807.
PRIDEiQ06807.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000026836; ENSBTAP00000026836; ENSBTAG00000020148.
GeneIDi280939.
KEGGibta:280939.

Organism-specific databases

CTDi7010.

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00830000128295.
HOGENOMiHOG000049232.
HOVERGENiHBG007316.
InParanoidiQ06807.
KOiK05121.
OMAiCHEDTGE.
OrthoDBiEOG7966FR.
TreeFamiTF317568.

Enzyme and pathway databases

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

Family and domain databases

Gene3Di2.60.40.10. 6 hits.
InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR003961. FN3_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamiPF00041. fn3. 3 hits.
PF10430. Ig_Tie2_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00181. EGF. 2 hits.
SM00060. FN3. 3 hits.
SM00220. S_TKc. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF49265. SSF49265. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00022. 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.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Tie-1 and tie-2 define another class of putative receptor tyrosine kinase genes expressed in early embryonic vascular system."
    Sato T.N., Qin Y., Kozak C.A., Andus K.L.
    Proc. Natl. Acad. Sci. U.S.A. 90:9355-9358(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Endothelial cell.

Entry informationi

Entry nameiTIE2_BOVIN
AccessioniPrimary (citable) accession number: Q06807
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: July 6, 2016
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.