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Protein

Angiopoietin-1 receptor

Gene

TEK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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

  • ATP binding Source: UniProtKB-KW
  • protein kinase activity Source: ProtInc
  • protein tyrosine kinase activity Source: UniProtKB
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • receptor activity Source: ProtInc
  • transmembrane receptor protein tyrosine kinase activity Source: ProtInc

GO - Biological processi

  • angiogenesis Source: UniProtKB
  • cell-cell signaling Source: ProtInc
  • definitive hemopoiesis Source: UniProtKB
  • endochondral ossification Source: Ensembl
  • endothelial cell proliferation Source: UniProtKB
  • glomerulus vasculature development Source: UniProtKB
  • heart development Source: UniProtKB
  • heart trabecula formation Source: UniProtKB
  • leukocyte migration Source: Reactome
  • MAPK cascade Source: Reactome
  • negative regulation of angiogenesis Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of endothelial cell apoptotic process Source: UniProtKB
  • negative regulation of inflammatory response Source: UniProtKB
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • positive regulation of actin cytoskeleton reorganization Source: UniProtKB
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of endothelial cell migration Source: UniProtKB
  • positive regulation of endothelial cell proliferation Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of focal adhesion assembly Source: UniProtKB
  • positive regulation of intracellular signal transduction Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of protein kinase B signaling Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein oligomerization Source: UniProtKB
  • regulation of endothelial cell apoptotic process Source: UniProtKB
  • regulation of establishment or maintenance of cell polarity Source: UniProtKB
  • regulation of vascular permeability Source: UniProtKB
  • response to cAMP Source: Ensembl
  • response to estrogen Source: Ensembl
  • response to hypoxia Source: Ensembl
  • response to peptide hormone Source: Ensembl
  • signal transduction Source: ProtInc
  • sprouting angiogenesis Source: UniProtKB
  • substrate adhesion-dependent cell spreading Source: UniProtKB
  • Tie signaling pathway Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Angiogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS04374-MONOMER.
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

HGNCiHGNC:11724. TEK.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 748ExtracellularSequence analysisAdd BLAST726
Transmembranei749 – 769HelicalSequence analysisAdd BLAST21
Topological domaini770 – 1124CytoplasmicSequence analysisAdd BLAST355

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB
  • basal plasma membrane Source: UniProtKB
  • basolateral plasma membrane Source: UniProtKB
  • cell-cell junction Source: UniProtKB
  • cell surface Source: UniProtKB
  • cytoplasm Source: UniProtKB-KW
  • cytoskeleton Source: UniProtKB-SubCell
  • extracellular region Source: UniProtKB-SubCell
  • focal adhesion Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: UniProtKB
  • membrane raft Source: UniProtKB
  • microvillus Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Dominantly inherited venous malformations (VMCM)3 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. 3 PublicationsCorresponds to variant rs80338908dbSNPEnsembl.1
Natural variantiVAR_066606897Y → C in VMCM; increased ligand-independent autophosphorylation and kinase activation. 1 PublicationCorresponds to variant rs80338909dbSNPEnsembl.1
Natural variantiVAR_008716897Y → S in VMCM; increased ligand-independent autophosphorylation and kinase activation. 2 PublicationsCorresponds to variant rs80338909dbSNPEnsembl.1
Natural variantiVAR_066607915R → H in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 PublicationCorresponds to variant rs387906745dbSNPEnsembl.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

May play a role in a range of diseases with a vascular component, including neovascularization of tumors, psoriasis and inflammation.

Mutagenesis

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

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7010.
MalaCardsiTEK.
MIMi600195. phenotype.
OpenTargetsiENSG00000120156.
Orphaneti2451. Mucocutaneous venous malformations.
PharmGKBiPA36441.

Chemistry databases

ChEMBLiCHEMBL4128.
DrugBankiDB00415. Ampicillin.
DB08901. Ponatinib.
DB08896. Regorafenib.
DB05294. Vandetanib.
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...)1 Publication1
Glycosylationi158N-linked (GlcNAc...)Sequence 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...)Sequence analysis1
Glycosylationi438N-linked (GlcNAc...)Sequence analysis1
Glycosylationi464N-linked (GlcNAc...)Sequence analysis1
Glycosylationi560N-linked (GlcNAc...)Sequence analysis1
Glycosylationi596N-linked (GlcNAc...)1 Publication1
Glycosylationi649N-linked (GlcNAc...)Sequence analysis1
Glycosylationi691N-linked (GlcNAc...)Sequence analysis1
Modified residuei860Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei992Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1102Phosphotyrosine; by autocatalysis1 Publication1
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

PaxDbiQ02763.
PeptideAtlasiQ02763.
PRIDEiQ02763.

PTM databases

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.
CleanExiHS_TEK.
ExpressionAtlasiQ02763. baseline and differential.
GenevisibleiQ02763. HS.

Organism-specific databases

HPAiCAB010359.
HPA011738.

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

WithEntry#Exp.IntActNotes
ANGPT2O151234EBI-2257090,EBI-2912111
PTPN12Q052092EBI-2257090,EBI-2266035
PTPRBP234673EBI-2257090,EBI-1265766
PTPRCP085753EBI-2257090,EBI-1341
PTPRJQ129132EBI-2257090,EBI-2264500
PTPRKQ152622EBI-2257090,EBI-474052
PTPROQ168272EBI-2257090,EBI-723739

Protein-protein interaction databases

BioGridi112869. 10 interactors.
DIPiDIP-6047N.
IntActiQ02763. 21 interactors.
STRINGi9606.ENSP00000369375.

Chemistry databases

BindingDBiQ02763.

Structurei

Secondary structure

11124
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 29Combined sources4
Beta strandi33 – 35Combined sources3
Beta strandi40 – 46Combined sources7
Beta strandi56 – 59Combined sources4
Turni61 – 63Combined sources3
Beta strandi64 – 66Combined sources3
Beta strandi74 – 76Combined sources3
Beta strandi80 – 88Combined sources9
Beta strandi98 – 106Combined sources9
Beta strandi109 – 119Combined sources11
Beta strandi123 – 125Combined sources3
Beta strandi127 – 133Combined sources7
Beta strandi139 – 145Combined sources7
Beta strandi153 – 157Combined sources5
Beta strandi160 – 165Combined sources6
Helixi167 – 169Combined sources3
Beta strandi172 – 178Combined sources7
Helixi183 – 185Combined sources3
Beta strandi187 – 193Combined sources7
Helixi198 – 200Combined sources3
Beta strandi202 – 208Combined sources7
Beta strandi215 – 217Combined sources3
Turni235 – 237Combined sources3
Beta strandi246 – 248Combined sources3
Beta strandi259 – 261Combined sources3
Turni271 – 276Combined sources6
Beta strandi279 – 281Combined sources3
Turni282 – 285Combined sources4
Beta strandi286 – 288Combined sources3
Helixi296 – 298Combined sources3
Beta strandi322 – 324Combined sources3
Turni325 – 327Combined sources3
Beta strandi328 – 330Combined sources3
Beta strandi361 – 366Combined sources6
Beta strandi369 – 373Combined sources5
Helixi380 – 382Combined sources3
Beta strandi383 – 386Combined sources4
Beta strandi396 – 400Combined sources5
Beta strandi405 – 408Combined sources4
Beta strandi411 – 414Combined sources4
Helixi416 – 418Combined sources3
Beta strandi420 – 428Combined sources9
Beta strandi431 – 439Combined sources9
Beta strandi816 – 818Combined sources3
Helixi821 – 823Combined sources3
Beta strandi825 – 831Combined sources7
Helixi833 – 835Combined sources3
Beta strandi837 – 845Combined sources9
Beta strandi848 – 858Combined sources11
Helixi864 – 866Combined sources3
Helixi868 – 876Combined sources9
Beta strandi888 – 894Combined sources7
Beta strandi897 – 902Combined sources6
Helixi910 – 915Combined sources6
Helixi919 – 922Combined sources4
Helixi924 – 929Combined sources6
Beta strandi932 – 936Combined sources5
Helixi938 – 957Combined sources20
Helixi967 – 969Combined sources3
Beta strandi970 – 972Combined sources3
Helixi974 – 976Combined sources3
Beta strandi978 – 980Combined sources3
Beta strandi986 – 989Combined sources4
Turni1002 – 1004Combined sources3
Helixi1007 – 1012Combined sources6
Helixi1017 – 1032Combined sources16
Turni1038 – 1041Combined sources4
Helixi1044 – 1050Combined sources7
Helixi1051 – 1053Combined sources3
Helixi1065 – 1074Combined sources10
Helixi1079 – 1081Combined sources3
Helixi1085 – 1097Combined sources13
Beta strandi1098 – 1100Combined sources3
Helixi1118 – 1120Combined sources3

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[»]
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
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.
GeneTreeiENSGT00810000125384.
HOGENOMiHOG000049232.
HOVERGENiHBG007316.
InParanoidiQ02763.
KOiK05121.
OMAiCHEDTGE.
OrthoDBiEOG091G00RL.
PhylomeDBiQ02763.
TreeFamiTF317568.

Family and domain databases

CDDicd00063. FN3. 2 hits.
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. 3 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. 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.
[Graphical view]

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

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

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_035714117K → N in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. 2 Publications1
Natural variantiVAR_041855148I → T.1 PublicationCorresponds to variant rs35969327dbSNPEnsembl.1
Natural variantiVAR_041856226A → V.1 PublicationCorresponds to variant rs35814893dbSNPEnsembl.1
Natural variantiVAR_048002346Q → P.4 PublicationsCorresponds to variant rs682632dbSNPEnsembl.1
Natural variantiVAR_048003391T → I.Corresponds to variant rs34032300dbSNPEnsembl.1
Natural variantiVAR_024578486V → I.1 PublicationCorresponds to variant rs1334811dbSNPEnsembl.1
Natural variantiVAR_041857600V → L.1 PublicationCorresponds to variant rs35030851dbSNPEnsembl.1
Natural variantiVAR_041858634L → F.1 PublicationCorresponds to variant rs35378598dbSNPEnsembl.1
Natural variantiVAR_041859676V → I.1 PublicationCorresponds to variant rs56367117dbSNPEnsembl.1
Natural variantiVAR_041860724A → T.1 PublicationCorresponds to variant rs4631561dbSNPEnsembl.1
Natural variantiVAR_006352849R → W in VMCM; increased ligand-independent autophosphorylation and kinase activation. 3 PublicationsCorresponds to variant rs80338908dbSNPEnsembl.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 rs80338909dbSNPEnsembl.1
Natural variantiVAR_008716897Y → S in VMCM; increased ligand-independent autophosphorylation and kinase activation. 2 PublicationsCorresponds to variant rs80338909dbSNPEnsembl.1
Natural variantiVAR_066607915R → H in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. 1 PublicationCorresponds to variant rs387906745dbSNPEnsembl.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
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, AL355432, AL355433 Genomic DNA. Translation: CAI16055.1.
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

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, AL355432, AL355433 Genomic DNA. Translation: CAI16055.1.
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[»]
ProteinModelPortaliQ02763.
SMRiQ02763.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112869. 10 interactors.
DIPiDIP-6047N.
IntActiQ02763. 21 interactors.
STRINGi9606.ENSP00000369375.

Chemistry databases

BindingDBiQ02763.
ChEMBLiCHEMBL4128.
DrugBankiDB00415. Ampicillin.
DB08901. Ponatinib.
DB08896. Regorafenib.
DB05294. Vandetanib.
GuidetoPHARMACOLOGYi1842.

PTM databases

iPTMnetiQ02763.
PhosphoSitePlusiQ02763.
UniCarbKBiQ02763.

Polymorphism and mutation databases

BioMutaiTEK.
DMDMi218511853.

Proteomic databases

PaxDbiQ02763.
PeptideAtlasiQ02763.
PRIDEiQ02763.

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.
GeneCardsiTEK.
GeneReviewsiTEK.
HGNCiHGNC:11724. TEK.
HPAiCAB010359.
HPA011738.
MalaCardsiTEK.
MIMi600195. phenotype.
600221. gene.
neXtProtiNX_Q02763.
OpenTargetsiENSG00000120156.
Orphaneti2451. Mucocutaneous venous malformations.
PharmGKBiPA36441.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS04374-MONOMER.
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.
PROiQ02763.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000120156.
CleanExiHS_TEK.
ExpressionAtlasiQ02763. baseline and differential.
GenevisibleiQ02763. HS.

Family and domain databases

CDDicd00063. FN3. 2 hits.
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. 3 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. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTIE2_HUMAN
AccessioniPrimary (citable) accession number: Q02763
Secondary accession number(s): A8K6W0
, B4DH20, B4DHD3, D3DRK5, E7EWI2, Q5TCU2, Q8IV34
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: December 16, 2008
Last modified: November 30, 2016
This is version 191 of the entry and version 2 of the sequence. [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 cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  8. 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.