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Protein

Angiopoietin-1 receptor

Gene

TEK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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 TIE1.10 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation6 Publications

Activity regulationi

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.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei855ATPCurated1
Active sitei964Proton acceptor1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi830 – 838ATPCurated9

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-210993 Tie2 Signaling
R-HSA-5673001 RAF/MAP kinase cascade
SignaLinkiQ02763
SIGNORiQ02763

Names & Taxonomyi

Protein namesi
Recommended name:
Angiopoietin-1 receptor (EC:2.7.10.1)
Alternative name(s):
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
Short name:
hTIE2
p140 TEK
CD_antigen: CD202b
Gene namesi
Name:TEK
Synonyms:TIE2, VMCM, VMCM1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000120156.20
HGNCiHGNC:11724 TEK
MIMi600221 gene
neXtProtiNX_Q02763

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 – 1124CytoplasmicSequence analysisAdd BLAST355

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Dominantly inherited venous malformations (VMCM)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn error of vascular morphogenesis characterized by dilated, serpiginous channels.
See also OMIM:600195
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_006352849R → W in VMCM; increased ligand-independent autophosphorylation and kinase activation; no effect on location at membrane. 4 PublicationsCorresponds to variant dbSNP:rs80338908EnsemblClinVar.1
Natural variantiVAR_066606897Y → C in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 PublicationCorresponds to variant dbSNP:rs80338909EnsemblClinVar.1
Natural variantiVAR_008716897Y → S in VMCM; also found in a patient with solitary sporadic venous malformations; increased ligand-independent autophosphorylation and kinase activation. 3 PublicationsCorresponds to variant dbSNP:rs80338909EnsemblClinVar.1
Natural variantiVAR_066607915R → H in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 PublicationCorresponds to variant dbSNP:rs387906745EnsemblClinVar.1
Natural variantiVAR_066608918R → C in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 Publication1
Natural variantiVAR_066609919V → L in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 Publication1
Natural variantiVAR_066610925A → S in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 Publication1
Natural variantiVAR_0666111100K → N in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 Publication1
Somatic mutations of TEK are associated with solitary and multiple sporadic venous malformations.1 Publication
May play a role in a range of diseases with a vascular component, including neovascularization of tumors, psoriasis and inflammation.
Glaucoma 3, primary congenital, E (GLC3E)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor.
See also OMIM:617272
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07804519 – 210Missing in GLC3E; formation of protein aggregates. 1 PublicationAdd BLAST192
Natural variantiVAR_078046233C → Y in GLC3E; enhanced proteasomal degradation. 1 Publication1
Natural variantiVAR_078047294K → N in GLC3E; unknown pathological significance; 10-fold decrease of Tyr-1102 phosphorylation; no effect on membrane location. 1 PublicationCorresponds to variant dbSNP:rs146169480Ensembl.1
Natural variantiVAR_078048611Y → C in GLC3E; reduced response to ligand; loss of ligand-induced phosphorylation; no effect on basal membrane location. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi224C → S: Reduces protein abundance. 1 Publication1
Mutagenesisi855K → R: Loss of kinase activity. 2 Publications1
Mutagenesisi1102Y → F: Abolishes interaction with SHC1. 1 Publication1

Keywords - Diseasei

Disease mutation, Glaucoma

Organism-specific databases

DisGeNETi7010
GeneReviewsiTEK
MalaCardsiTEK
MIMi600195 phenotype
617272 phenotype
OpenTargetsiENSG00000120156
Orphaneti2451 Mucocutaneous venous malformations
PharmGKBiPA36441

Chemistry databases

ChEMBLiCHEMBL4128
DrugBankiDB00415 Ampicillin
DB08221 N-{4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDE
DB08901 Ponatinib
DB08896 Regorafenib
DB05294 Vandetanib
DB05153 XL184
GuidetoPHARMACOLOGYi1842

Polymorphism and mutation databases

BioMutaiTEK
DMDMi218511853

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 221 PublicationAdd BLAST22
ChainiPRO_000002447423 – 1124Angiopoietin-1 receptorAdd BLAST1102

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi44 ↔ 1021 Publication
Glycosylationi140N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi158N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi211 ↔ 2201 Publication
Disulfide bondi224 ↔ 2331 Publication
Disulfide bondi227 ↔ 2401 Publication
Disulfide bondi242 ↔ 2511 Publication
Disulfide bondi255 ↔ 2641 Publication
Disulfide bondi268 ↔ 2741 Publication
Disulfide bondi280 ↔ 2871 Publication
Disulfide bondi289 ↔ 2981 Publication
Disulfide bondi302 ↔ 3111 Publication
Disulfide bondi315 ↔ 3231 Publication
Disulfide bondi317 ↔ 3291 Publication
Disulfide bondi331 ↔ 3401 Publication
Disulfide bondi370 ↔ 4241 Publication
Glycosylationi399N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi438N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi464N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi560N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi596N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi649N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi691N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei860Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei992Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1102Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei1108Phosphotyrosine; by autocatalysis1 Publication1

Post-translational modificationi

Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2).1 Publication
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-992 in the kinase activation loop is phosphorylated first, followed by autophosphorylation at Tyr-1108 and at additional tyrosine residues. ANGPT1-induced phosphorylation is impaired during hypoxia, due to increased expression of ANGPT2. Phosphorylation is important for interaction with GRB14, PIK3R1 and PTPN11. Phosphorylation at Tyr-1102 is important for interaction with SHC1, GRB2 and GRB7. Phosphorylation at Tyr-1108 is important for interaction with DOK2 and for coupling to downstream signal transduction pathways in endothelial cells. Dephosphorylated by PTPRB.2 Publications
Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ02763
PaxDbiQ02763
PeptideAtlasiQ02763
PRIDEiQ02763
ProteomicsDBi58121
58122 [Q02763-2]
58123 [Q02763-3]

PTM databases

GlyConnecti769
iPTMnetiQ02763
PhosphoSitePlusiQ02763
UniCarbKBiQ02763

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiENSG00000120156 Expressed in 192 organ(s), highest expression level in metanephric glomerulus
CleanExiHS_TEK
ExpressionAtlasiQ02763 baseline and differential
GenevisibleiQ02763 HS

Organism-specific databases

HPAiCAB010359
HPA073265

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 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).13 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112869, 18 interactors
DIPiDIP-6047N
IntActiQ02763, 22 interactors
MINTiQ02763
STRINGi9606.ENSP00000369375

Chemistry databases

BindingDBiQ02763

Structurei

Secondary structure

11124
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ02763
SMRiQ02763
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ02763

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 – 636Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST92
Domaini641 – 735Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST95
Domaini824 – 1096Protein 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.1 Publication

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
GeneTreeiENSGT00810000125384
HOGENOMiHOG000049232
HOVERGENiHBG007316
InParanoidiQ02763
KOiK05121
OMAiAIEYAPH
OrthoDBiEOG091G00RL
PhylomeDBiQ02763
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, 3 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, 3 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

Sequences (3+)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q02763-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MDSLASLVLC GVSLLLSGTV EGAMDLILIN SLPLVSDAET SLTCIASGWR
60 70 80 90 100
PHEPITIGRD FEALMNQHQD PLEVTQDVTR EWAKKVVWKR EKASKINGAY
110 120 130 140 150
FCEGRVRGEA IRIRTMKMRQ QASFLPATLT MTVDKGDNVN ISFKKVLIKE
160 170 180 190 200
EDAVIYKNGS FIHSVPRHEV PDILEVHLPH AQPQDAGVYS ARYIGGNLFT
210 220 230 240 250
SAFTRLIVRR CEAQKWGPEC NHLCTACMNN GVCHEDTGEC ICPPGFMGRT
260 270 280 290 300
CEKACELHTF GRTCKERCSG QEGCKSYVFC LPDPYGCSCA TGWKGLQCNE
310 320 330 340 350
ACHPGFYGPD CKLRCSCNNG EMCDRFQGCL CSPGWQGLQC EREGIQRMTP
360 370 380 390 400
KIVDLPDHIE VNSGKFNPIC KASGWPLPTN EEMTLVKPDG TVLHPKDFNH
410 420 430 440 450
TDHFSVAIFT IHRILPPDSG VWVCSVNTVA GMVEKPFNIS VKVLPKPLNA
460 470 480 490 500
PNVIDTGHNF AVINISSEPY FGDGPIKSKK LLYKPVNHYE AWQHIQVTNE
510 520 530 540 550
IVTLNYLEPR TEYELCVQLV RRGEGGEGHP GPVRRFTTAS IGLPPPRGLN
560 570 580 590 600
LLPKSQTTLN LTWQPIFPSS EDDFYVEVER RSVQKSDQQN IKVPGNLTSV
610 620 630 640 650
LLNNLHPREQ YVVRARVNTK AQGEWSEDLT AWTLSDILPP QPENIKISNI
660 670 680 690 700
THSSAVISWT ILDGYSISSI TIRYKVQGKN EDQHVDVKIK NATITQYQLK
710 720 730 740 750
GLEPETAYQV DIFAENNIGS SNPAFSHELV TLPESQAPAD LGGGKMLLIA
760 770 780 790 800
ILGSAGMTCL TVLLAFLIIL QLKRANVQRR MAQAFQNVRE EPAVQFNSGT
810 820 830 840 850
LALNRKVKNN PDPTIYPVLD WNDIKFQDVI GEGNFGQVLK ARIKKDGLRM
860 870 880 890 900
DAAIKRMKEY ASKDDHRDFA GELEVLCKLG HHPNIINLLG ACEHRGYLYL
910 920 930 940 950
AIEYAPHGNL LDFLRKSRVL ETDPAFAIAN STASTLSSQQ LLHFAADVAR
960 970 980 990 1000
GMDYLSQKQF IHRDLAARNI LVGENYVAKI ADFGLSRGQE VYVKKTMGRL
1010 1020 1030 1040 1050
PVRWMAIESL NYSVYTTNSD VWSYGVLLWE IVSLGGTPYC GMTCAELYEK
1060 1070 1080 1090 1100
LPQGYRLEKP LNCDDEVYDL MRQCWREKPY ERPSFAQILV SLNRMLEERK
1110 1120
TYVNTTLYEK FTYAGIDCSA EEAA
Length:1,124
Mass (Da):125,830
Last modified:December 16, 2008 - v2
Checksum:iE739DEC3E4FEB124
GO
Isoform 2 (identifier: Q02763-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     300-342: Missing.

Show »
Length:1,081
Mass (Da):121,048
Checksum:iFA9BF050B49AB557
GO
Isoform 3 (identifier: Q02763-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     18-121: Missing.
     300-342: Missing.
     788-788: Missing.

Show »
Length:976
Mass (Da):109,141
Checksum:iCE8D06A4F93D48E0
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B5A954B5A954_HUMAN
Angiopoietin-1 receptor
TEK
468Annotation score:
E5RIV9E5RIV9_HUMAN
Angiopoietin-1 receptor
TEK
468Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti536F → L in BAG58094 (PubMed:14702039).Curated1
Sequence conflicti695T → I in AAA61139 (PubMed:8382358).Curated1
Sequence conflicti939 – 940QQ → HH in AAH35514 (PubMed:15489334).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07804519 – 210Missing in GLC3E; formation of protein aggregates. 1 PublicationAdd BLAST192
Natural variantiVAR_035714117K → N in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. 2 Publications1
Natural variantiVAR_041855148I → T1 PublicationCorresponds to variant dbSNP:rs35969327EnsemblClinVar.1
Natural variantiVAR_041856226A → V1 PublicationCorresponds to variant dbSNP:rs35814893EnsemblClinVar.1
Natural variantiVAR_078046233C → Y in GLC3E; enhanced proteasomal degradation. 1 Publication1
Natural variantiVAR_078047294K → N in GLC3E; unknown pathological significance; 10-fold decrease of Tyr-1102 phosphorylation; no effect on membrane location. 1 PublicationCorresponds to variant dbSNP:rs146169480Ensembl.1
Natural variantiVAR_048002346Q → P4 PublicationsCorresponds to variant dbSNP:rs682632Ensembl.1
Natural variantiVAR_048003391T → I. Corresponds to variant dbSNP:rs34032300EnsemblClinVar.1
Natural variantiVAR_024578486V → I1 PublicationCorresponds to variant dbSNP:rs1334811EnsemblClinVar.1
Natural variantiVAR_041857600V → L1 PublicationCorresponds to variant dbSNP:rs35030851EnsemblClinVar.1
Natural variantiVAR_078048611Y → C in GLC3E; reduced response to ligand; loss of ligand-induced phosphorylation; no effect on basal membrane location. 1 Publication1
Natural variantiVAR_041858634L → F1 PublicationCorresponds to variant dbSNP:rs35378598EnsemblClinVar.1
Natural variantiVAR_041859676V → I1 PublicationCorresponds to variant dbSNP:rs56367117Ensembl.1
Natural variantiVAR_041860724A → T1 PublicationCorresponds to variant dbSNP:rs4631561EnsemblClinVar.1
Natural variantiVAR_006352849R → W in VMCM; increased ligand-independent autophosphorylation and kinase activation; no effect on location at membrane. 4 PublicationsCorresponds to variant dbSNP:rs80338908EnsemblClinVar.1
Natural variantiVAR_041861883P → A in an ovarian serous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_066606897Y → C in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 PublicationCorresponds to variant dbSNP:rs80338909EnsemblClinVar.1
Natural variantiVAR_078049897Y → F Found in a patient with multiple sporadic venous malformations; increased ligand-independent autophosphorylation; the hyperphosphorylation increases when associated with Leu-915. 1 Publication1
Natural variantiVAR_078050897Y → H Found in a patient with solitary sporadic venous malformations; increased ligand-independent autophosphorylation. 1 Publication1
Natural variantiVAR_008716897Y → S in VMCM; also found in a patient with solitary sporadic venous malformations; increased ligand-independent autophosphorylation and kinase activation. 3 PublicationsCorresponds to variant dbSNP:rs80338909EnsemblClinVar.1
Natural variantiVAR_078051914L → F Found in patients with solitary and multiple sporadic venous malformations; increased ligand-independent autophosphorylation; novel location at endoplasmic reticulum and Golgi apparatus; partially retained at endoplasmic reticulum and Golgi apparatus. 1 Publication1
Natural variantiVAR_078052915R → C Found in a patient with solitary sporadic venous malformations; increased ligand-independent autophosphorylation. 1 Publication1
Natural variantiVAR_066607915R → H in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 PublicationCorresponds to variant dbSNP:rs387906745EnsemblClinVar.1
Natural variantiVAR_078053915R → L Found in a patient with multiple sporadic venous malformations; increased ligand-independent autophosphorylation; the autophosphorylation increases when associated with Phe-897. 1 Publication1
Natural variantiVAR_078054917S → I Found in a patient with solitary sporadic venous malformations; increased ligand-independent autophosphorylation. 1 Publication1
Natural variantiVAR_066608918R → C in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 Publication1
Natural variantiVAR_066609919V → L in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 Publication1
Natural variantiVAR_066610925A → S in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 Publication1
Natural variantiVAR_0666111100K → N in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 Publication1
Natural variantiVAR_0418621124A → V in a renal clear cell carcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04213718 – 121Missing in isoform 3. 1 PublicationAdd BLAST104
Alternative sequenceiVSP_042138300 – 342Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_042139788Missing in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L06139 mRNA Translation: AAA61139.1
AK291775 mRNA Translation: BAF84464.1
AK294887 mRNA Translation: BAG57981.1
AK295043 mRNA Translation: BAG58094.1
AL133411 Genomic DNA No translation available.
AL355432 Genomic DNA No translation available.
AL355433 Genomic DNA No translation available.
CH471071 Genomic DNA Translation: EAW58571.1
CH471071 Genomic DNA Translation: EAW58572.1
BC035514 mRNA Translation: AAH35514.2
CCDSiCCDS6519.1 [Q02763-1]
CCDS75825.1 [Q02763-2]
CCDS78389.1 [Q02763-3]
PIRiI58388
RefSeqiNP_000450.2, NM_000459.4
NP_001277006.1, NM_001290077.1
NP_001277007.1, NM_001290078.1
UniGeneiHs.89640

Genome annotation databases

EnsembliENST00000380036; ENSP00000369375; ENSG00000120156 [Q02763-1]
ENST00000406359; ENSP00000383977; ENSG00000120156 [Q02763-2]
ENST00000519097; ENSP00000430686; ENSG00000120156 [Q02763-3]
GeneIDi7010
KEGGihsa:7010
UCSCiuc003zqi.5 human [Q02763-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L06139 mRNA Translation: AAA61139.1
AK291775 mRNA Translation: BAF84464.1
AK294887 mRNA Translation: BAG57981.1
AK295043 mRNA Translation: BAG58094.1
AL133411 Genomic DNA No translation available.
AL355432 Genomic DNA No translation available.
AL355433 Genomic DNA No translation available.
CH471071 Genomic DNA Translation: EAW58571.1
CH471071 Genomic DNA Translation: EAW58572.1
BC035514 mRNA Translation: AAH35514.2
CCDSiCCDS6519.1 [Q02763-1]
CCDS75825.1 [Q02763-2]
CCDS78389.1 [Q02763-3]
PIRiI58388
RefSeqiNP_000450.2, NM_000459.4
NP_001277006.1, NM_001290077.1
NP_001277007.1, NM_001290078.1
UniGeneiHs.89640

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FVRX-ray2.20A/B808-1124[»]
2GY5X-ray2.90A23-445[»]
2GY7X-ray3.70B23-445[»]
2OO8X-ray2.20X808-1124[»]
2OSCX-ray2.80A808-1124[»]
2P4IX-ray2.50A/B808-1124[»]
2WQBX-ray2.95A802-1124[»]
3BEAX-ray2.02A917-935[»]
3L8PX-ray2.40A808-1124[»]
4K0VX-ray4.51A23-542[»]
4X3JX-ray2.50A802-1122[»]
5MYAX-ray2.90A/B443-742[»]
5MYBX-ray2.60A/B443-742[»]
5UTKX-ray2.50A/B442-741[»]
ProteinModelPortaliQ02763
SMRiQ02763
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112869, 18 interactors
DIPiDIP-6047N
IntActiQ02763, 22 interactors
MINTiQ02763
STRINGi9606.ENSP00000369375

Chemistry databases

BindingDBiQ02763
ChEMBLiCHEMBL4128
DrugBankiDB00415 Ampicillin
DB08221 N-{4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDE
DB08901 Ponatinib
DB08896 Regorafenib
DB05294 Vandetanib
DB05153 XL184
GuidetoPHARMACOLOGYi1842

PTM databases

GlyConnecti769
iPTMnetiQ02763
PhosphoSitePlusiQ02763
UniCarbKBiQ02763

Polymorphism and mutation databases

BioMutaiTEK
DMDMi218511853

Proteomic databases

EPDiQ02763
PaxDbiQ02763
PeptideAtlasiQ02763
PRIDEiQ02763
ProteomicsDBi58121
58122 [Q02763-2]
58123 [Q02763-3]

Protocols and materials databases

DNASUi7010
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380036; ENSP00000369375; ENSG00000120156 [Q02763-1]
ENST00000406359; ENSP00000383977; ENSG00000120156 [Q02763-2]
ENST00000519097; ENSP00000430686; ENSG00000120156 [Q02763-3]
GeneIDi7010
KEGGihsa:7010
UCSCiuc003zqi.5 human [Q02763-1]

Organism-specific databases

CTDi7010
DisGeNETi7010
EuPathDBiHostDB:ENSG00000120156.20
GeneCardsiTEK
GeneReviewsiTEK
HGNCiHGNC:11724 TEK
HPAiCAB010359
HPA073265
MalaCardsiTEK
MIMi600195 phenotype
600221 gene
617272 phenotype
neXtProtiNX_Q02763
OpenTargetsiENSG00000120156
Orphaneti2451 Mucocutaneous venous malformations
PharmGKBiPA36441
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0200 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00810000125384
HOGENOMiHOG000049232
HOVERGENiHBG007316
InParanoidiQ02763
KOiK05121
OMAiAIEYAPH
OrthoDBiEOG091G00RL
PhylomeDBiQ02763
TreeFamiTF317568

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-210993 Tie2 Signaling
R-HSA-5673001 RAF/MAP kinase cascade
SignaLinkiQ02763
SIGNORiQ02763

Miscellaneous databases

ChiTaRSiTEK human
EvolutionaryTraceiQ02763
GeneWikiiTEK_tyrosine_kinase
GenomeRNAii7010
PROiPR:Q02763
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000120156 Expressed in 192 organ(s), highest expression level in metanephric glomerulus
CleanExiHS_TEK
ExpressionAtlasiQ02763 baseline and differential
GenevisibleiQ02763 HS

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, 3 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, 3 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
ProtoNetiSearch...

Entry informationi

Entry nameiTIE2_HUMAN
AccessioniPrimary (citable) accession number: Q02763
Secondary accession number(s): A8K6W0
, B4DH20, B4DHD3, D3DRK5, E7EWI2, Q5TCU2, Q8IV34
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: December 16, 2008
Last modified: September 12, 2018
This is version 205 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  8. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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