Q02858 (TIE2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Angiopoietin-1 receptor
EC=2.7.10.1

Alternative name(s):
Endothelial tyrosine kinase
HYK
STK1
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=mTIE2
p140 TEK
CD_antigen=CD202b

Gene names

Name:	Tek
Synonyms:	Hyk, Tie-2, Tie2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1122 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1, SHC1 and TIE1. Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.15 Ref.16 Ref.18
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.8
Enzyme regulation	Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-990 on the kinase activation loop By similarity.
Subunit structure	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. Ref.10 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18
Subcellular location	Cell membrane; Single-pass type I membrane protein. Cell junction By similarity. Cell junction › focal adhesion By similarity. Cytoplasm › cytoskeleton By similarity. Secreted By similarity. Note: Recruited to cell-cell contacts in quiescent endothelial cells. Colocalizes with the actin cytoskeleton and at actin stress fibers during cell spreading. Recruited to the lower surface of migrating cells, especially the rear end of the cell. Proteolytic processing gives rise to a soluble extracellular domain that is secreted By similarity.
Tissue specificity	Specifically expressed in developing vascular endothelial cells. Abundantly expressed in lung and heart, moderately in brain, liver and kidney, and weakly in thymus, spleen and testis. Ref.6
Developmental stage	Expression detectable in day 8.5 embryos.
Domain	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. Ref.14
Post-translational modification	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-990 in the kinase activation loop is phosphorylated first, followed by autophosphorylation at Tyr-1106 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-1100 is important for interaction with GRB2 and GRB7. Phosphorylation at Tyr-1106 is important for interaction with DOK2 and for coupling to downstream signal transduction pathways in endothelial cells. Dephosphorylated by PTPRB. Ref.12 Ref.15 Ref.16 Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation By similarity. Ref.12 Ref.15 Ref.16
Disruption phenotype	Embryonically lethal. Embryos die at about 10 dpc, due to strongly decreased numbers of blood vessel endothelial cells, leading to severe hemorrhaging, and due to defects in heart trabeculae development. Mice display a general malformation of the vascular network with defective sprouting and dilated blood vessels. Ref.8 Ref.9
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Tie subfamily. Contains 3 EGF-like domains. Contains 3 fibronectin type-III domains. Contains 2 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cytoplasm Cytoskeleton Membrane Secreted
Domain	EGF-like domain Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Tie receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB cell-cell adhesion Inferred from mutant phenotype PubMed 9683559. Source: MGI cell-matrix adhesion Inferred from mutant phenotype PubMed 9683559. Source: MGI endothelial cell proliferation Inferred from mutant phenotype Ref.8. Source: UniProtKB heart trabecula formation Inferred from mutant phenotype Ref.8. Source: UniProtKB hemopoiesis Inferred from mutant phenotype PubMed 15260986PubMed 9846489. Source: MGI negative regulation of angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of endothelial cell apoptotic process Inferred from mutant phenotype Ref.13. Source: UniProtKB patterning of blood vessels Traceable author statement PubMed 20299672. Source: DFLAT peptidyl-tyrosine phosphorylation Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of endothelial cell migration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of focal adhesion assembly Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of peptidyl-serine phosphorylation Inferred from genetic interaction PubMed 19409199. Source: MGI positive regulation of phosphatidylinositol 3-kinase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein kinase B signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of vascular endothelial growth factor receptor signaling pathway Traceable author statement PubMed 20406889. Source: DFLAT protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of endothelial cell proliferation Traceable author statement PubMed 20406889. Source: DFLAT regulation of establishment or maintenance of cell polarity Inferred from sequence or structural similarity. Source: UniProtKB response to retinoic acid Inferred from direct assay PubMed 18439490. Source: BHF-UCL sprouting angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB substrate adhesion-dependent cell spreading Inferred from sequence or structural similarity. Source: UniProtKB vasculogenesis Inferred from mutant phenotype Ref.8. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell focal adhesion Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from sequence model Ref.1. Source: MGI integral to plasma membrane Inferred from electronic annotation. Source: InterPro plasma membrane Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein tyrosine kinase activity Inferred from direct assay Ref.8. Source: UniProtKB receptor activity Inferred from physical interaction PubMed 8980223. Source: MGI transmembrane receptor protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	By similarity
	Chain	23 – 1122	1100	Angiopoietin-1 receptor		PRO_0000024475
Regions
	Topological domain	23 – 746	724	Extracellular Potential
	Transmembrane	747 – 767	21	Helical; Potential
	Topological domain	768 – 1122	355	Cytoplasmic Potential
	Domain	44 – 123	80	Ig-like C2-type 1
	Domain	210 – 252	43	EGF-like 1
	Domain	254 – 299	46	EGF-like 2
	Domain	301 – 341	41	EGF-like 3
	Domain	350 – 440	91	Ig-like C2-type 2
	Domain	445 – 535	91	Fibronectin type-III 1
	Domain	542 – 632	91	Fibronectin type-III 2
	Domain	638 – 730	93	Fibronectin type-III 3
	Domain	822 – 1094	273	Protein kinase
	Nucleotide binding	828 – 836	9	ATP By similarity
Sites
	Active site	962	1	Proton acceptor By similarity
	Binding site	853	1	ATP By similarity
Amino acid modifications
	Modified residue	858	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	990	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1100	1	Phosphotyrosine; by autocatalysis Probable
	Modified residue	1106	1	Phosphotyrosine; by autocatalysis Ref.15
	Glycosylation	140	1	N-linked (GlcNAc...) Potential
	Glycosylation	158	1	N-linked (GlcNAc...) Potential
	Glycosylation	399	1	N-linked (GlcNAc...) Potential
	Glycosylation	438	1	N-linked (GlcNAc...) Potential
	Glycosylation	464	1	N-linked (GlcNAc...) Potential
	Glycosylation	558	1	N-linked (GlcNAc...) Potential
	Glycosylation	595	1	N-linked (GlcNAc...) Potential
	Glycosylation	648	1	N-linked (GlcNAc...) Potential
	Glycosylation	690	1	N-linked (GlcNAc...) Potential
	Disulfide bond	44 ↔ 102		By similarity
	Disulfide bond	211 ↔ 220		By similarity
	Disulfide bond	224 ↔ 233		By similarity
	Disulfide bond	227 ↔ 240		By similarity
	Disulfide bond	242 ↔ 251		By similarity
	Disulfide bond	255 ↔ 264		By similarity
	Disulfide bond	268 ↔ 274		By similarity
	Disulfide bond	280 ↔ 287		By similarity
	Disulfide bond	289 ↔ 298		By similarity
	Disulfide bond	302 ↔ 311		By similarity
	Disulfide bond	315 ↔ 323		By similarity
	Disulfide bond	317 ↔ 329		By similarity
	Disulfide bond	331 ↔ 340		By similarity
	Disulfide bond	370 ↔ 424		By similarity
Experimental info
	Mutagenesis	853	1	K → A: Loss of kinase activity. Ref.8 Ref.15
	Mutagenesis	1100	1	Y → F: Reduced levels of autophosphorylation. Abolishes interaction with GRB2 and GRB7. Abolishes phosphorylation of GRB7 and PIK3R1. Ref.10 Ref.11 Ref.15
	Mutagenesis	1106	1	Y → F: Reduced levels of autophosphorylation. Ref.15
	Sequence conflict	161 – 171	11	FIHSVPRHEVP → LHPLSAPGMKYL in BAA02883. Ref.3
	Sequence conflict	538	1	S → C in CAA47857. Ref.2
	Sequence conflict	736	1	A → G in CAA47857. Ref.2
	Sequence conflict	736	1	A → G in AAB28663. Ref.4
	Sequence conflict	745 – 761	17	MLLIA…TCITV → DATHSHPWVWNDFASPC in BAA02883. Ref.3
	Sequence conflict	786	1	N → NV in BAA02883. Ref.3
	Sequence conflict	786	1	N → NV no nucleotide entry Ref.6
	Sequence conflict	913	1	R → G in BAA02883. Ref.3
	Sequence conflict	925 – 931	7	AIANSTA → CHRQQYS in BAA02883. Ref.3
	Sequence conflict	1117	1	S → P in BAA02883. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q02858 [UniParc]. Last modified February 1, 1995. Version 2. Checksum: F879623D103FFE96	FASTA	1,122	125,701
	10 20 30 40 50 60 MDSLAGLVLC GVSLLLYGVV EGAMDLILIN SLPLVSDAET SLTCIASGWH PHEPITIGRD 70 80 90 100 110 120 FEALMNQHQD PLEVTQDVTR EWAKKVVWKR EKASKINGAY FCEGRVRGQA IRIRTMKMRQ 130 140 150 160 170 180 QASFLPATLT MTVDRGDNVN ISFKKVLIKE EDAVIYKNGS FIHSVPRHEV PDILEVHLPH 190 200 210 220 230 240 AQPQDAGVYS ARYIGGNLFT SAFTRLIVRR CEAQKWGPDC SRPCTTCKNN GVCHEDTGEC 250 260 270 280 290 300 ICPPGFMGRT CEKACEPHTF GRTCKERCSG PEGCKSYVFC LPDPYGCSCA TGWRGLQCNE 310 320 330 340 350 360 ACPSGYYGPD CKLRCHCTNE EICDRFQGCL CSQGWQGLQC EKEGRPRMTP QIEDLPDHIE 370 380 390 400 410 420 VNSGKFNPIC KASGWPLPTS EEMTLVKPDG TVLQPNDFNY TDRFSVAIFT VNRVLPPDSG 430 440 450 460 470 480 VWVCSVNTVA GMVEKPFNIS VKVLPEPLHA PNVIDTGHNF AIINISSEPY FGDGPIKSKK 490 500 510 520 530 540 LFYKPVNQAW KYIEVTNEIF TLNYLEPRTD YELCVQLARP GEGGEGHPGP VRRFTTASIG 550 560 570 580 590 600 LPPPRGLSLL PKSQTALNLT WQPIFTNSED EFYVEVERRS LQTTSDQQNI KVPGNLTSVL 610 620 630 640 650 660 LSNLVPREQY TVRARVNTKA QGEWSEELRA WTLSDILPPQ PENIKISNIT DSTAMVSWTI 670 680 690 700 710 720 VDGYSISSII IRYKVQGKNE DQHIDVKIKN ATVTQYQLKG LEPETTYHVD IFAENNIGSS 730 740 750 760 770 780 NPAFSHELRT LPHSPASADL GGGKMLLIAI LGSAGMTCIT VLLAFLIMLQ LKRANVQRRM 790 800 810 820 830 840 AQAFQNREEP AVQFNSGTLA LNRKAKNNPD PTIYPVLDWN DIKFQDVIGE GNFGQVLKAR 850 860 870 880 890 900 IKKDGLRMDA AIKRMKEYAS KDDHRDFAGE LEVLCKLGHH PNIINLLGAC EHRGYLYLAI 910 920 930 940 950 960 EYAPHGNLLD FLRKSRVLET DPAFAIANST ASTLSSQQLL HFAADVARGM DYLSQKQFIH 970 980 990 1000 1010 1020 RDLAARNILV GENYIAKIAD FGLSRGQEVY VKKTMGRLPV RWMAIESLNY SVYTTNSDVW 1030 1040 1050 1060 1070 1080 SYGVLLWEIV SLGGTPYCGM TCAELYEKLP QGYRLEKPLN CDDEVYDLMR QCWREKPYER 1090 1100 1110 1120 PSFAQILVSL NRMLEERKTY VNTTLYEKFT YAGIDCSAEE AA

References

[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]. Strain: BALB/c. Tissue: Lung.
[2]	"The endothelial-specific receptor tyrosine kinase, tek, is a member of a new subfamily of receptors." Dumont D.J., Gradwol G.J., Fong G.-H., Auerbach R., Breitman M.L. Oncogene 8:1293-1301(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: CD-1. Tissue: Embryonic heart.
[3]	"A novel tyrosine kinase, hyk, expressed in murine embryonic stem cells." Horita K., Yagi T., Kohmura N., Tomooka Y., Ikawa Y., Aizawa S. Biochem. Biophys. Res. Commun. 189:1747-1753(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Embryonic stem cell.
[4]	"Tie2, a putative protein tyrosine kinase from a new class of cell surface receptor." Runting A.S., Stacker S.A., Wilks A.F. Growth Factors 9:99-105(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[5]	"Expression of tie-2, a member of a novel family of receptor tyrosine kinases, in the endothelial cell lineage." Schnuerch H., Risau W. Development 119:957-968(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Molecular cloning and characterization of mouse TIE and TEK receptor tyrosine kinase genes and their expression in hematopoietic stem cells." Iwama A., Hamaguchi I., Hashiyama M., Murayama Y., Yasunaga K., Suda T. Biochem. Biophys. Res. Commun. 195:301-309(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Hematopoietic stem cell.
[7]	"Tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors." Dumont D.J., Yamaguchi T.P., Conlon R.A., Rossant J., Breitman M.L. Oncogene 7:1471-1480(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 822-1122. Strain: CD-1. Tissue: Embryonic heart.
[8]	"Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo." Dumont D.J., Gradwohl G., Fong G.H., Puri M.C., Gertsenstein M., Auerbach A., Breitman M.L. Genes Dev. 8:1897-1909(1994) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, MUTAGENESIS OF LYS-853, CATALYTIC ACTIVITY, FUNCTION.
[9]	"Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation." Sato T.N., Tozawa Y., Deutsch U., Wolburg-Buchholz K., Fujiwara Y., Gendron-Maguire M., Gridley T., Wolburg H., Risau W., Qin Y. Nature 376:70-74(1995) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[10]	"Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt." Kontos C.D., Stauffer T.P., Yang W.P., York J.D., Huang L., Blanar M.A., Meyer T., Peters K.G. Mol. Cell. Biol. 18:4131-4140(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PIK3R1, MUTAGENESIS OF TYR-1100, FUNCTION IN ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE AND AKT1.
[11]	"Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration." Jones N., Master Z., Jones J., Bouchard D., Gunji Y., Sasaki H., Daly R., Alitalo K., Dumont D.J. J. Biol. Chem. 274:30896-30905(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRB2; GRB7, GRB14, PTPN11/SHP2 AND PIK3R1, FUNCTION IN PHOSPHORYLATION OF GRB7 AND PIK3R1, MUTAGENESIS OF TYR-1100.
[12]	"Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the angiopoietin receptor Tie-2." Fachinger G., Deutsch U., Risau W. Oncogene 18:5948-5953(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPRB.
[13]	"Rescue of the early vascular defects in Tek/Tie2 null mice reveals an essential survival function." Jones N., Voskas D., Master Z., Sarao R., Jones J., Dumont D.J. EMBO Rep. 2:438-445(2001) [PubMed] [Europe PMC] [Abstract] Cited for: ANTI-APOPTOTIC FUNCTION.
[14]	"Angiopoietin-1 and angiopoietin-2 share the same binding domains in the Tie-2 receptor involving the first Ig-like loop and the epidermal growth factor-like repeats." Fiedler U., Krissl T., Koidl S., Weiss C., Koblizek T., Deutsch U., Martiny-Baron G., Marme D., Augustin H.G. J. Biol. Chem. 278:1721-1727(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ANGPT1 AND ANGPT2, DOMAIN.
[15]	"A unique autophosphorylation site on Tie2/Tek mediates Dok-R phosphotyrosine binding domain binding and function." Jones N., Chen S.H., Sturk C., Master Z., Tran J., Kerbel R.S., Dumont D.J. Mol. Cell. Biol. 23:2658-2668(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-1100 AND TYR-1106, MUTAGENESIS OF LYS-853; TYR-1100 AND TYR-1106, FUNCTION IN DOK2 PHOSPHORYLATION, INTERACTION WITH DOK2.
[16]	"Biological characterization of angiopoietin-3 and angiopoietin-4." Lee H.J., Cho C.H., Hwang S.J., Choi H.H., Kim K.T., Ahn S.Y., Kim J.H., Oh J.L., Lee G.M., Koh G.Y. FASEB J. 18:1200-1208(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS ANGPT4 RECEPTOR AND IN ACTIVATION OF AKT1, INTERACTION WITH ANGPT4, AUTOPHOSPHORYLATION.
[17]	"VE-PTP controls blood vessel development by balancing Tie-2 activity." Winderlich M., Keller L., Cagna G., Broermann A., Kamenyeva O., Kiefer F., Deutsch U., Nottebaum A.F., Vestweber D. J. Cell Biol. 185:657-671(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTPRB.
[18]	"Tyrosine phosphorylation of Grb14 by Tie2." Sturk C., Dumont D.J. Cell Commun. Signal. 8:30-30(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRB14, FUNCTION IN GRB14 PHOSPHORYLATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X71426 mRNA. Translation: CAA50557.1. X67553 mRNA. Translation: CAA47857.1. D13738 mRNA. Translation: BAA02883.1. S67051 mRNA. Translation: AAB28663.1.
IPI	IPI00622082.
PIR	I54237. JH0771. JN0712.
UniGene	Mm.14313.
3D structure databases
ProteinModelPortal	Q02858.
SMR	Q02858. Positions 23-723, 784-1119.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-6050N.
PTM databases
PhosphoSite	Q02858.
Proteomic databases
PaxDb	Q02858.
PRIDE	Q02858.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000071168; ENSMUSP00000071162; ENSMUSG00000006386.
Organism-specific databases
MGI	MGI:98664. Tek.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00670000097694.
HOGENOM	HOG000049232.
HOVERGEN	HBG007316.
Enzyme and pathway databases
BRENDA	2.7.10.1. 3474.
Reactome	REACT_89750. Hemostasis.
Gene expression databases
ArrayExpress	Q02858.
Bgee	Q02858.
CleanEx	MM_TEK.
Genevestigator	Q02858.
GermOnline	ENSMUSG00000006386. Mus musculus.
Family and domain databases
Gene3D	2.60.40.10. 5 hits.
InterPro	IPR000742. EG-like_dom. IPR013032. EGF-like_CS. IPR002049. EGF_laminin. IPR003961. Fibronectin_type3. IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_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]
Pfam	PF00041. fn3. 3 hits. PF10430. Ig_Tie2_1. 1 hit. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SMART	SM00181. EGF. 1 hit. SM00180. EGF_Lam. 1 hit. SM00060. FN3. 3 hits. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 3 hits. SSF56112. Kinase_like. 1 hit.
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. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q02858.
ChEMBL	CHEMBL5199.
SOURCE	Search...

Entry information

Entry name

TIE2_MOUSE

Accession

Primary (citable) accession number: Q02858

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 132 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program