Q02763 (TIE2_HUMAN) 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
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 names

Name:	TEK
Synonyms:	TIE2, VMCM, VMCM1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1124 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.7 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.21 Ref.22 Ref.26
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.1 Ref.9 Ref.11 Ref.13 Ref.14 Ref.21
Enzyme regulation	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. Ref.9 Ref.26 Ref.27 Ref.29 Ref.30 Ref.31
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 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). Ref.7 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.18 Ref.19
Subcellular location	Cell membrane; Single-pass type I membrane protein. Cell junction. Cell junction › focal adhesion. Cytoplasm › cytoskeleton. Secreted. 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. Ref.8 Ref.14 Ref.15 Ref.16 Ref.18
Tissue specificity	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. Ref.1 Ref.8
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. Ref.12
Post-translational modification	Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2). 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. Ref.7 Ref.9 Ref.11 Ref.13 Ref.14 Ref.16 Ref.17 Ref.21 Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation. Ref.7 Ref.9 Ref.11 Ref.13 Ref.14 Ref.16 Ref.17 Ref.21
Involvement in disease	Dominantly inherited venous malformations (VMCM) [MIM:600195]: An error of vascular morphogenesis characterized by dilated, serpiginous channels. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.22 Ref.26 Ref.33 Ref.34 Ref.37 May play a role in a range of diseases with a vascular component, including neovascularization of tumors, psoriasis and inflammation. Ref.22 Ref.26
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
Biological process	Angiogenesis
Cellular component	Cell junction Cell membrane Cytoplasm Cytoskeleton Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
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	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Tie receptor signaling pathway Inferred from direct assay Ref.12Ref.21. Source: UniProtKB blood coagulation Traceable author statement. Source: Reactome cell-cell adhesion Inferred from electronic annotation. Source: Compara cell-cell signaling Traceable author statement Ref.33. Source: ProtInc cell-matrix adhesion Inferred from electronic annotation. Source: Compara definitive hemopoiesis Traceable author statement Ref.22. Source: UniProtKB endothelial cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB glomerulus vasculature development Inferred from sequence or structural similarity. Source: UniProtKB heart trabecula formation Inferred from sequence or structural similarity. Source: UniProtKB leukocyte migration Traceable author statement. Source: Reactome negative regulation of angiogenesis Inferred from mutant phenotype Ref.15. Source: UniProtKB negative regulation of endothelial cell apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of inflammatory response Traceable author statement Ref.22. Source: UniProtKB peptidyl-tyrosine phosphorylation Inferred from direct assay Ref.9. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from direct assay PubMed 19615361. Source: UniProtKB positive regulation of actin cytoskeleton reorganization Inferred from mutant phenotype Ref.10. Source: UniProtKB positive regulation of angiogenesis Inferred from direct assay Ref.12. Source: UniProtKB positive regulation of endothelial cell migration Inferred from direct assay Ref.12. Source: UniProtKB positive regulation of endothelial cell proliferation Traceable author statement Ref.15. Source: UniProtKB positive regulation of focal adhesion assembly Inferred from mutant phenotype Ref.15. Source: UniProtKB positive regulation of peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of phosphatidylinositol 3-kinase activity Inferred from mutant phenotype Ref.10Ref.15. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase cascade Inferred from mutant phenotype Ref.10Ref.15Ref.21. Source: UniProtKB positive regulation of protein kinase B signaling cascade Inferred from direct assay PubMed 19615361. Source: UniProtKB positive regulation of protein phosphorylation Inferred from direct assay Ref.12. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.9. Source: UniProtKB protein oligomerization Inferred from direct assay PubMed 19424712. Source: UniProtKB regulation of establishment or maintenance of cell polarity Inferred from mutant phenotype Ref.16. Source: UniProtKB regulation of vascular permeability Traceable author statement Ref.22Ref.15. Source: UniProtKB sprouting angiogenesis Inferred from mutant phenotype Ref.13. Source: UniProtKB substrate adhesion-dependent cell spreading Inferred from mutant phenotype Ref.16. Source: UniProtKB
Cellular_component	apical plasma membrane Inferred from direct assay PubMed 19424712. Source: UniProtKB basal plasma membrane Inferred from direct assay Ref.15. Source: UniProtKB cell surface Inferred from direct assay Ref.18. Source: UniProtKB cell-cell junction Inferred from direct assay Ref.15. Source: UniProtKB 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 plasma membrane Inferred from direct assay Ref.18. Source: UniProtKB membrane raft Inferred from direct assay PubMed 19615361. Source: UniProtKB microvillus Inferred from direct assay PubMed 19424712. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW transmembrane receptor protein tyrosine kinase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ANGPT2	O15123	4	EBI-2257090,EBI-2912111
PTPN12	Q05209	2	EBI-2257090,EBI-2266035
PTPRB	P23467	3	EBI-2257090,EBI-1265766
PTPRC	P08575	3	EBI-2257090,EBI-1341
PTPRJ	Q12913	2	EBI-2257090,EBI-2264500
PTPRK	Q15262	2	EBI-2257090,EBI-474052
PTPRO	Q16827	2	EBI-2257090,EBI-723739

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q02763-1)

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.

Isoform 2 (identifier: Q02763-2)

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

Isoform 3 (identifier: Q02763-3)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.6

Chain

23 – 1124

1102

Angiopoietin-1 receptor

PRO_0000024474

Regions

Topological domain

23 – 748

726

Extracellular Potential

Transmembrane

749 – 769

21

Helical; Potential

Topological domain

770 – 1124

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 – 537

93

Fibronectin type-III 1

Domain

544 – 633

90

Fibronectin type-III 2

Domain

639 – 730

92

Fibronectin type-III 3

Domain

824 – 1096

273

Protein kinase

Nucleotide binding

830 – 838

9

ATP Probable

Sites

Active site

964

1

Proton acceptor Probable

Binding site

855

1

ATP Probable

Amino acid modifications

Modified residue

860

1

Phosphotyrosine; by autocatalysis Ref.9

Modified residue

992

1

Phosphotyrosine; by autocatalysis Ref.9

Modified residue

1102

1

Phosphotyrosine; by autocatalysis Ref.13

Modified residue

1108

1

Phosphotyrosine; by autocatalysis Ref.9

Glycosylation

140

1

N-linked (GlcNAc...) Ref.28

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

560

1

N-linked (GlcNAc...) Potential

Glycosylation

596

1

N-linked (GlcNAc...) Ref.20

Glycosylation

649

1

N-linked (GlcNAc...) Potential

Glycosylation

691

1

N-linked (GlcNAc...) Potential

Disulfide bond

44 ↔ 102

Ref.28

Disulfide bond

211 ↔ 220

Ref.28

Disulfide bond

224 ↔ 233

Ref.28

Disulfide bond

227 ↔ 240

Ref.28

Disulfide bond

242 ↔ 251

Ref.28

Disulfide bond

255 ↔ 264

Ref.28

Disulfide bond

268 ↔ 274

Ref.28

Disulfide bond

280 ↔ 287

Ref.28

Disulfide bond

289 ↔ 298

Ref.28

Disulfide bond

302 ↔ 311

Ref.28

Disulfide bond

315 ↔ 323

Ref.28

Disulfide bond

317 ↔ 329

Ref.28

Disulfide bond

331 ↔ 340

Ref.28

Disulfide bond

370 ↔ 424

Ref.28

Natural variations

Alternative sequence

18 – 121

104

Missing in isoform 3.

VSP_042137

Alternative sequence

300 – 342

43

Missing in isoform 2 and isoform 3.

VSP_042138

Alternative sequence

788

1

Missing in isoform 3.

VSP_042139

Natural variant

117

1

K → N in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. Ref.35 Ref.36

VAR_035714

Natural variant

148

1

I → T. Ref.36
Corresponds to variant rs35969327 [ dbSNP | Ensembl ].

VAR_041855

Natural variant

226

1

A → V. Ref.36
Corresponds to variant rs35814893 [ dbSNP | Ensembl ].

VAR_041856

Natural variant

346

1

Q → P. Ref.1 Ref.2 Ref.4 Ref.5
Corresponds to variant rs682632 [ dbSNP | Ensembl ].

VAR_048002

Natural variant

391

1

T → I.
Corresponds to variant rs34032300 [ dbSNP | Ensembl ].

VAR_048003

Natural variant

486

1

V → I. Ref.36
Corresponds to variant rs1334811 [ dbSNP | Ensembl ].

VAR_024578

Natural variant

600

1

V → L. Ref.36
Corresponds to variant rs35030851 [ dbSNP | Ensembl ].

VAR_041857

Natural variant

634

1

L → F. Ref.36
Corresponds to variant rs35378598 [ dbSNP | Ensembl ].

VAR_041858

Natural variant

676

1

V → I. Ref.36
Corresponds to variant rs56367117 [ dbSNP | Ensembl ].

VAR_041859

Natural variant

724

1

A → T. Ref.36
Corresponds to variant rs4631561 [ dbSNP | Ensembl ].

VAR_041860

Natural variant

849

1

R → W in VMCM; increased ligand-independent autophosphorylation and kinase activation. Ref.33 Ref.34 Ref.37

VAR_006352

Natural variant

883

1

P → A in an ovarian serous carcinoma sample; somatic mutation. Ref.36

VAR_041861

Natural variant

897

1

Y → C in VMCM; increased ligand-independent autophosphorylation and kinase activation. Ref.37

VAR_066606

Natural variant

897

1

Y → S in VMCM; increased ligand-independent autophosphorylation and kinase activation. Ref.34 Ref.37

VAR_008716

Natural variant

915

1

R → H in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. Ref.37

VAR_066607

Natural variant

918

1

R → C in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. Ref.37

VAR_066608

Natural variant

919

1

V → L in VMCM; increased ligand-independent autophosphorylation and kinase activation. Ref.37

VAR_066609

Natural variant

925

1

A → S in VMCM; increased ligand-independent autophosphorylation and kinase activation. Ref.37

VAR_066610

Natural variant

1100

1

K → N in VMCM; strongly increased ligand-independent autophosphorylation and kinase activation. Ref.37

VAR_066611

Natural variant

1124

1

A → V in a renal clear cell carcinoma sample; somatic mutation. Ref.36

VAR_041862

Experimental info

Mutagenesis

855

1

K → R: Loss of kinase activity. Ref.11 Ref.14

Mutagenesis

1102

1

Y → F: Abolishes interaction with SHC1. Ref.13

Sequence conflict

536

1

F → L in BAG58094. Ref.2

Sequence conflict

695

1

T → I in AAA61139. Ref.1

Sequence conflict

939 – 940

2

QQ → HH in AAH35514. Ref.5

Secondary structure

1

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1124

Helix Strand Turn

Details...

Beta strand

26 – 29

4

Beta strand

33 – 35

3

Beta strand

40 – 46

7

Beta strand

56 – 59

4

Turn

61 – 63

3

Beta strand

64 – 66

3

Beta strand

74 – 76

3

Beta strand

80 – 88

9

Beta strand

98 – 106

9

Beta strand

109 – 119

11

Beta strand

123 – 125

3

Beta strand

127 – 133

7

Beta strand

139 – 145

7

Beta strand

153 – 157

5

Beta strand

160 – 165

6

Helix

167 – 169

3

Beta strand

172 – 178

7

Helix

183 – 185

3

Beta strand

187 – 193

7

Helix

198 – 200

3

Beta strand

202 – 208

7

Beta strand

215 – 217

3

Turn

235 – 237

3

Beta strand

246 – 248

3

Beta strand

259 – 261

3

Turn

271 – 276

6

Beta strand

279 – 281

3

Turn

282 – 285

4

Beta strand

286 – 288

3

Helix

296 – 298

3

Beta strand

322 – 324

3

Turn

325 – 327

3

Beta strand

328 – 330

3

Beta strand

361 – 366

6

Beta strand

369 – 373

5

Helix

380 – 382

3

Beta strand

383 – 386

4

Beta strand

396 – 400

5

Beta strand

405 – 408

4

Beta strand

411 – 414

4

Helix

416 – 418

3

Beta strand

420 – 428

9

Beta strand

431 – 439

9

Beta strand

816 – 818

3

Helix

821 – 823

3

Beta strand

825 – 831

7

Helix

833 – 835

3

Beta strand

837 – 845

9

Beta strand

848 – 858

11

Helix

868 – 876

9

Beta strand

888 – 894

7

Beta strand

897 – 902

6

Helix

910 – 915

6

Helix

919 – 922

4

Helix

924 – 929

6

Beta strand

932 – 936

5

Helix

938 – 957

20

Helix

967 – 969

3

Beta strand

970 – 972

3

Helix

974 – 976

3

Beta strand

978 – 980

3

Beta strand

986 – 989

4

Turn

1002 – 1004

3

Helix

1007 – 1012

6

Helix

1017 – 1032

16

Turn

1038 – 1041

4

Helix

1044 – 1050

7

Helix

1051 – 1053

3

Helix

1065 – 1074

10

Helix

1079 – 1081

3

Helix

1085 – 1097

13

Beta strand

1098 – 1100

3

Helix

1118 – 1120

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 16, 2008. Version 2. Checksum: E739DEC3E4FEB124	FASTA	1,124	125,830
	10 20 30 40 50 60 MDSLASLVLC GVSLLLSGTV EGAMDLILIN SLPLVSDAET SLTCIASGWR PHEPITIGRD 70 80 90 100 110 120 FEALMNQHQD PLEVTQDVTR EWAKKVVWKR EKASKINGAY FCEGRVRGEA IRIRTMKMRQ 130 140 150 160 170 180 QASFLPATLT MTVDKGDNVN ISFKKVLIKE EDAVIYKNGS FIHSVPRHEV PDILEVHLPH 190 200 210 220 230 240 AQPQDAGVYS ARYIGGNLFT SAFTRLIVRR CEAQKWGPEC NHLCTACMNN GVCHEDTGEC 250 260 270 280 290 300 ICPPGFMGRT CEKACELHTF GRTCKERCSG QEGCKSYVFC LPDPYGCSCA TGWKGLQCNE 310 320 330 340 350 360 ACHPGFYGPD CKLRCSCNNG EMCDRFQGCL CSPGWQGLQC EREGIQRMTP KIVDLPDHIE 370 380 390 400 410 420 VNSGKFNPIC KASGWPLPTN EEMTLVKPDG TVLHPKDFNH TDHFSVAIFT IHRILPPDSG 430 440 450 460 470 480 VWVCSVNTVA GMVEKPFNIS VKVLPKPLNA PNVIDTGHNF AVINISSEPY FGDGPIKSKK 490 500 510 520 530 540 LLYKPVNHYE AWQHIQVTNE IVTLNYLEPR TEYELCVQLV RRGEGGEGHP GPVRRFTTAS 550 560 570 580 590 600 IGLPPPRGLN LLPKSQTTLN LTWQPIFPSS EDDFYVEVER RSVQKSDQQN IKVPGNLTSV 610 620 630 640 650 660 LLNNLHPREQ YVVRARVNTK AQGEWSEDLT AWTLSDILPP QPENIKISNI THSSAVISWT 670 680 690 700 710 720 ILDGYSISSI TIRYKVQGKN EDQHVDVKIK NATITQYQLK GLEPETAYQV DIFAENNIGS 730 740 750 760 770 780 SNPAFSHELV TLPESQAPAD LGGGKMLLIA ILGSAGMTCL TVLLAFLIIL QLKRANVQRR 790 800 810 820 830 840 MAQAFQNVRE EPAVQFNSGT LALNRKVKNN PDPTIYPVLD WNDIKFQDVI GEGNFGQVLK 850 860 870 880 890 900 ARIKKDGLRM DAAIKRMKEY ASKDDHRDFA GELEVLCKLG HHPNIINLLG ACEHRGYLYL 910 920 930 940 950 960 AIEYAPHGNL LDFLRKSRVL ETDPAFAIAN STASTLSSQQ LLHFAADVAR GMDYLSQKQF 970 980 990 1000 1010 1020 IHRDLAARNI LVGENYVAKI ADFGLSRGQE VYVKKTMGRL PVRWMAIESL NYSVYTTNSD 1030 1040 1050 1060 1070 1080 VWSYGVLLWE IVSLGGTPYC GMTCAELYEK LPQGYRLEKP LNCDDEVYDL MRQCWREKPY 1090 1100 1110 1120 ERPSFAQILV SLNRMLEERK TYVNTTLYEK FTYAGIDCSA EEAA
	Isoform 2 [UniParc]. Checksum: FA9BF050B49AB557	FASTA	1,081	121,048
	10 20 30 40 50 60 MDSLASLVLC GVSLLLSGTV EGAMDLILIN SLPLVSDAET SLTCIASGWR PHEPITIGRD 70 80 90 100 110 120 FEALMNQHQD PLEVTQDVTR EWAKKVVWKR EKASKINGAY FCEGRVRGEA IRIRTMKMRQ 130 140 150 160 170 180 QASFLPATLT MTVDKGDNVN ISFKKVLIKE EDAVIYKNGS FIHSVPRHEV PDILEVHLPH 190 200 210 220 230 240 AQPQDAGVYS ARYIGGNLFT SAFTRLIVRR CEAQKWGPEC NHLCTACMNN GVCHEDTGEC 250 260 270 280 290 300 ICPPGFMGRT CEKACELHTF GRTCKERCSG QEGCKSYVFC LPDPYGCSCA TGWKGLQCNE 310 320 330 340 350 360 GIQRMTPKIV DLPDHIEVNS GKFNPICKAS GWPLPTNEEM TLVKPDGTVL HPKDFNHTDH 370 380 390 400 410 420 FSVAIFTIHR ILPPDSGVWV CSVNTVAGMV EKPFNISVKV LPKPLNAPNV IDTGHNFAVI 430 440 450 460 470 480 NISSEPYFGD GPIKSKKLLY KPVNHYEAWQ HIQVTNEIVT LNYLEPRTEY ELCVQLVRRG 490 500 510 520 530 540 EGGEGHPGPV RRFTTASIGL PPPRGLNLLP KSQTTLNLTW QPIFPSSEDD FYVEVERRSV 550 560 570 580 590 600 QKSDQQNIKV PGNLTSVLLN NLHPREQYVV RARVNTKAQG EWSEDLTAWT LSDILPPQPE 610 620 630 640 650 660 NIKISNITHS SAVISWTILD GYSISSITIR YKVQGKNEDQ HVDVKIKNAT ITQYQLKGLE 670 680 690 700 710 720 PETAYQVDIF AENNIGSSNP AFSHELVTLP ESQAPADLGG GKMLLIAILG SAGMTCLTVL 730 740 750 760 770 780 LAFLIILQLK RANVQRRMAQ AFQNVREEPA VQFNSGTLAL NRKVKNNPDP TIYPVLDWND 790 800 810 820 830 840 IKFQDVIGEG NFGQVLKARI KKDGLRMDAA IKRMKEYASK DDHRDFAGEL EVLCKLGHHP 850 860 870 880 890 900 NIINLLGACE HRGYLYLAIE YAPHGNLLDF LRKSRVLETD PAFAIANSTA STLSSQQLLH 910 920 930 940 950 960 FAADVARGMD YLSQKQFIHR DLAARNILVG ENYVAKIADF GLSRGQEVYV KKTMGRLPVR 970 980 990 1000 1010 1020 WMAIESLNYS VYTTNSDVWS YGVLLWEIVS LGGTPYCGMT CAELYEKLPQ GYRLEKPLNC 1030 1040 1050 1060 1070 1080 DDEVYDLMRQ CWREKPYERP SFAQILVSLN RMLEERKTYV NTTLYEKFTY AGIDCSAEEA A
	Isoform 3 [UniParc]. Checksum: CE8D06A4F93D48E0	FASTA	976	109,141
	10 20 30 40 50 60 MDSLASLVLC GVSLLLSASF LPATLTMTVD KGDNVNISFK KVLIKEEDAV IYKNGSFIHS 70 80 90 100 110 120 VPRHEVPDIL EVHLPHAQPQ DAGVYSARYI GGNLFTSAFT RLIVRRCEAQ KWGPECNHLC 130 140 150 160 170 180 TACMNNGVCH EDTGECICPP GFMGRTCEKA CELHTFGRTC KERCSGQEGC KSYVFCLPDP 190 200 210 220 230 240 YGCSCATGWK GLQCNEGIQR MTPKIVDLPD HIEVNSGKFN PICKASGWPL PTNEEMTLVK 250 260 270 280 290 300 PDGTVLHPKD FNHTDHFSVA IFTIHRILPP DSGVWVCSVN TVAGMVEKPF NISVKVLPKP 310 320 330 340 350 360 LNAPNVIDTG HNFAVINISS EPYFGDGPIK SKKLLYKPVN HYEAWQHIQV TNEIVTLNYL 370 380 390 400 410 420 EPRTEYELCV QLVRRGEGGE GHPGPVRRFT TASIGLPPPR GLNLLPKSQT TLNLTWQPIF 430 440 450 460 470 480 PSSEDDFYVE VERRSVQKSD QQNIKVPGNL TSVLLNNLHP REQYVVRARV NTKAQGEWSE 490 500 510 520 530 540 DLTAWTLSDI LPPQPENIKI SNITHSSAVI SWTILDGYSI SSITIRYKVQ GKNEDQHVDV 550 560 570 580 590 600 KIKNATITQY QLKGLEPETA YQVDIFAENN IGSSNPAFSH ELVTLPESQA PADLGGGKML 610 620 630 640 650 660 LIAILGSAGM TCLTVLLAFL IILQLKRANV QRRMAQAFQN REEPAVQFNS GTLALNRKVK 670 680 690 700 710 720 NNPDPTIYPV LDWNDIKFQD VIGEGNFGQV LKARIKKDGL RMDAAIKRMK EYASKDDHRD 730 740 750 760 770 780 FAGELEVLCK LGHHPNIINL LGACEHRGYL YLAIEYAPHG NLLDFLRKSR VLETDPAFAI 790 800 810 820 830 840 ANSTASTLSS QQLLHFAADV ARGMDYLSQK QFIHRDLAAR NILVGENYVA KIADFGLSRG 850 860 870 880 890 900 QEVYVKKTMG RLPVRWMAIE SLNYSVYTTN SDVWSYGVLL WEIVSLGGTP YCGMTCAELY 910 920 930 940 950 960 EKLPQGYRLE KPLNCDDEVY DLMRQCWREK PYERPSFAQI LVSLNRMLEE RKTYVNTTLY 970 EKFTYAGIDC SAEEAA

References

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[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT PRO-346.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT PRO-346. Tissue: Pancreas.
[6]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-37.
[7]	"Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis." Maisonpierre P.C., Suri C., Jones P.F., Bartunkova S., Wiegand S.J., Radziejewski C., Compton D.L., McClain J., Aldrich T.H., Papadopoulos N., Daly T.J., Davis S., Sato T.N., Yancopoulos G.D. Science 277:55-60(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS RECEPTOR FOR ANGPT1 AND ANGPT2, INTERACTION WITH ANGPT1 AND ANGPT2, AUTOPHOSPHORYLATION.
[8]	"Identification of a soluble form of the angiopoietin receptor TIE-2 released from endothelial cells and present in human blood." Reusch P., Barleon B., Weindel K., Martiny-Baron G., Godde A., Siemeister G., Marme D. Angiogenesis 4:123-131(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, TISSUE SPECIFICITY.
[9]	"Mechanistic effects of autophosphorylation on receptor tyrosine kinase catalysis: enzymatic characterization of Tie2 and phospho-Tie2." Murray B.W., Padrique E.S., Pinko C., McTigue M.A. Biochemistry 40:10243-10253(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, MASS SPECTROMETRY, PHOSPHORYLATION AT TYR-860; TYR-992 AND TYR-1108.
[10]	"Tie-2-dependent activation of RhoA and Rac1 participates in endothelial cell motility triggered by angiopoietin-1." Cascone I., Audero E., Giraudo E., Napione L., Maniero F., Philips M.R., Collard J.G., Serini G., Bussolino F. Blood 102:2482-2490(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN REGULATION OF PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; ENDOTHELIAL CELL MIGRATION AND REORGANIZATION OF THE ACTIN CYTOSKELETON.
[11]	"The antiinflammatory endothelial tyrosine kinase Tie2 interacts with a novel nuclear factor-kappaB inhibitor ABIN-2." Hughes D.P., Marron M.B., Brindle N.P. Circ. Res. 92:630-636(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNIP2, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-855.
[12]	"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 IN REGULATION OF ANGIOGENESIS; CELL SURVIVAL; CELL MIGRATION AND ACTIVATION OF AKT1, DOMAIN, INTERACTION WITH ANGPT1; ANGPT2 AND ANGPT4.
[13]	"Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells." Audero E., Cascone I., Maniero F., Napione L., Arese M., Lanfrancone L., Bussolino F. J. Biol. Chem. 279:13224-13233(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS ANGPT1 RECEPTOR IN PHOSPHORYLATION OF SHC1 AND PIK3R1; REGULATION OF CELL MIGRATION AND ANGIOGENESIS, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-1102, PHOSPHORYLATION AT TYR-1102, CATALYTIC ACTIVITY, INTERACTION WITH SHC1.
[14]	"Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2." Saharinen P., Kerkela K., Ekman N., Marron M., Brindle N., Lee G.M., Augustin H., Koh G.Y., Alitalo K. J. Cell Biol. 169:239-243(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TIE1, SUBCELLULAR LOCATION, FUNCTION AS RECEPTOR FOR ANGPT1 IN PHOSPHORYLATION OF TIE1, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-855.
[15]	"Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1." Fukuhara S., Sako K., Minami T., Noda K., Kim H.Z., Kodama T., Shibuya M., Takakura N., Koh G.Y., Mochizuki N. Nat. Cell Biol. 10:513-526(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS ANGPT1 RECEPTOR IN ACTIVATION OF AKT1 OR MAPK1/ERK2 AND MAPK3/ERK1; REGULATION OF ENDOTHELIAL CELL MIGRATION AND CELL SPREADING, SUBCELLULAR LOCATION.
[16]	"Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts." Saharinen P., Eklund L., Miettinen J., Wirkkala R., Anisimov A., Winderlich M., Nottebaum A., Vestweber D., Deutsch U., Koh G.Y., Olsen B.R., Alitalo K. Nat. Cell Biol. 10:527-537(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS ANGPT1 RECEPTOR IN ACTIVATION OF AKT1 OR MAPK1/ERK2 AND MAPK3/ERK1; REGULATION OF ENDOTHELIAL CELL MIGRATION AND REGULATION OF FOCAL ADHESION ASSEMBLY, INTERACTION WITH TIE1, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION.
[17]	"Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells." Yacyshyn O.K., Lai P.F.H., Forse K., Teichert-Kuliszewska K., Jurasz P., Stewart D.J. Angiogenesis 12:25-33(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPRB.
[18]	"Angiopoietin-1-induced ubiquitylation of Tie2 by c-Cbl is required for internalization and degradation." Wehrle C., Van Slyke P., Dumont D.J. Biochem. J. 423:375-380(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CBL, SUBCELLULAR LOCATION, UBIQUITINATION.
[19]	"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.
[20]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-596, MASS SPECTROMETRY. Tissue: Liver.
[21]	"Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium." Yuan H.T., Khankin E.V., Karumanchi S.A., Parikh S.M. Mol. Cell. Biol. 29:2011-2022(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS RECEPTOR FOR ANGPT1 AND ANGPT2 IN ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE AND AKT1; STIMULATION OF ENDOTHELIAL CELL SURVIVAL AND MIGRATION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION.
[22]	"Tie2: a journey from normal angiogenesis to cancer and beyond." Martin V., Liu D., Fueyo J., Gomez-Manzano C. Histol. Histopathol. 23:773-780(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION; INTERACTION WITH EFFECTOR AND SCAFFOLDING PROTEINS, ROLE IN DISEASE.
[23]	"Tie2 is tied at the cell-cell contacts and to extracellular matrix by angiopoietin-1." Fukuhara S., Sako K., Noda K., Nagao K., Miura K., Mochizuki N. Exp. Mol. Med. 41:133-139(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON SUBCELLULAR LOCATION AND CONTEXT-SPECIFIC SIGNALING.
[24]	"Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system." Augustin H.G., Koh G.Y., Thurston G., Alitalo K. Nat. Rev. Mol. Cell Biol. 10:165-177(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[25]	"Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis." Fukuhara S., Sako K., Noda K., Zhang J., Minami M., Mochizuki N. Histol. Histopathol. 25:387-396(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[26]	"Targeting the ANGPT-TIE2 pathway in malignancy." Huang H., Bhat A., Woodnutt G., Lappe R. Nat. Rev. Cancer 10:575-585(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON SIGNALING, ENZYME REGULATION, ROLE IN DISEASE.
[27]	"Structure of the Tie2 RTK domain: self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail." Shewchuk L.M., Hassell A.M., Ellis B., Holmes W.D., Davis R., Horne E.L., Kadwell S.H., McKee D.D., Moore J.T. Structure 8:1105-1113(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 808-1124, ACTIVE SITE, ENZYME REGULATION, PREDICTION OF ATP-BINDING REGION.
[28]	"Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex." Barton W.A., Tzvetkova-Robev D., Miranda E.P., Kolev M.V., Rajashankar K.R., Himanen J.P., Nikolov D.B. Nat. Struct. Mol. Biol. 13:524-532(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 23-445 ALONE AND IN COMPLEX WITH ANGPT2, GLYCOSYLATION AT ASN-140, DISULFIDE BONDS.
[29]	"Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors." Hodous B.L., Geuns-Meyer S.D., Hughes P.E., Albrecht B.K., Bellon S., Caenepeel S., Cee V.J., Chaffee S.C., Emery M., Fretland J., Gallant P., Gu Y., Johnson R.E., Kim J.L., Long A.M., Morrison M., Olivieri P.R., Patel V.F. , Polverino A., Rose P., Wang L., Zhao H. Bioorg. Med. Chem. Lett. 17:2886-2889(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 808-1124 IN COMPLEX WITH TRIAZINE DERIVATIVE, ENZYME REGULATION.
[30]	"Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine Tie-2 kinase inhibitor." Hodous B.L., Geuns-Meyer S.D., Hughes P.E., Albrecht B.K., Bellon S., Bready J., Caenepeel S., Cee V.J., Chaffee S.C., Coxon A., Emery M., Fretland J., Gallant P., Gu Y., Hoffman D., Johnson R.E., Kendall R., Kim J.L. , Long A.M., Morrison M., Olivieri P.R., Patel V.F., Polverino A., Rose P., Tempest P., Wang L., Whittington D.A., Zhao H. J. Med. Chem. 50:611-626(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 808-1124 IN COMPLEX WITH TRIAZINE DERIVATIVE, ENZYME REGULATION.
[31]	"Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with activity against Tie-2 in vitro and in vivo." Luke R.W., Ballard P., Buttar D., Campbell L., Curwen J., Emery S.C., Griffen A.M., Hassall L., Hayter B.R., Jones C.D., McCoull W., Mellor M., Swain M.L., Tucker J.A. Bioorg. Med. Chem. Lett. 19:6670-6674(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 802-1124 IN COMPLEX WITH THIAZOLOPYRIMIDINE DERIVATIVE, ENZYME REGULATION.
[32]	"Crystal structure of cytoplasmic kinase domain of Tie2 complexed with inhibitor CEP11207." Fedorov A.A., Fedorov E.V., Pauletti D., Meyer S.L., Hudkins R.L., Almo S.C. Submitted (JAN-2010) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 808-1124 IN COMPLEX WITH CEP11207.
[33]	"Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2." Vikkula M., Boon L.M., Carraway K.L. III, Calvert J.T., Diamonti A.J., Goumnerov B., Pasyk K.A., Marchuk D.A., Warman M.L., Cantley L.C., Mulliken J.B., Olse B.R. Cell 87:1181-1190(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT VMCM TRP-849.
[34]	"Allelic and locus heterogeneity in inherited venous malformations." Calvert J.T., Riney T.J., Kontos C.D., Cha E.H., Prieto V.G., Shea C.R., Berg J.N., Nevin N.C., Simpson S.A., Pasyk K.A., Speer M.C., Peters K.G., Marchuk D.A. Hum. Mol. Genet. 8:1279-1289(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VMCM TRP-849 AND SER-897.
[35]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-117.
[36]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-117; THR-148; VAL-226; ILE-486; LEU-600; PHE-634; ILE-676; THR-724; ALA-883 AND VAL-1124.
[37]	"Hereditary cutaneomucosal venous malformations are caused by TIE2 mutations with widely variable hyper-phosphorylating effects." Wouters V., Limaye N., Uebelhoer M., Irrthum A., Boon L.M., Mulliken J.B., Enjolras O., Baselga E., Berg J., Dompmartin A., Ivarsson S.A., Kangesu L., Lacassie Y., Murphy J., Teebi A.S., Penington A., Rieu P., Vikkula M. Eur. J. Hum. Genet. 18:414-420(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VMCM TRP-849; CYS-897; HIS-915; CYS-918; LEU-919; SER-925 AND ASN-1100, CHARACTERIZATION OF VARIANTS VMCM TRP-849; SER-897; HIS-915; CYS-918; LEU-919; SER-925 AND ASN-1100.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00412829.
IPI00979987.
IPI01012241.

PIR

I58388.

RefSeq

NP_000450.2. NM_000459.3.

UniGene

Hs.89640.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FVR	X-ray	2.20	A/B	808-1124	[»]
2GY5	X-ray	2.90	A	23-445	[»]
2GY7	X-ray	3.70	B	23-445	[»]
2OO8	X-ray	2.20	X	808-1124	[»]
2OSC	X-ray	2.80	A	808-1124	[»]
2P4I	X-ray	2.50	A/B	808-1124	[»]
2WQB	X-ray	2.95	A	802-1124	[»]
3BEA	X-ray	2.02	A	917-935	[»]
3L8P	X-ray	2.40	A	808-1124	[»]

ProteinModelPortal

Q02763.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6047N.

IntAct

Q02763. 18 interactions.

STRING

9606.ENSP00000383977.

PTM databases

PhosphoSite

Q02763.

Polymorphism databases

DMDM

218511853.

Proteomic databases

PaxDb

Q02763.

PRIDE

Q02763.

Protocols and materials databases

DNASU

7010.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380036; ENSP00000369375; ENSG00000120156.
ENST00000406359; ENSP00000383977; ENSG00000120156.
ENST00000488798; ENSP00000430233; ENSG00000120156.
ENST00000519097; ENSP00000430686; ENSG00000120156.

GeneID

7010.

KEGG

hsa:7010.

UCSC

uc003zqj.1. human.

Organism-specific databases

CTD

7010.

GeneCards

GC09P027109.

HGNC

HGNC:11724. TEK.

HPA

CAB010359.
HPA011738.

MIM

600195. phenotype.
600221. gene.

neXtProt

NX_Q02763.

Orphanet

2451. Mucocutaneous venous malformations.

PharmGKB

PA36441.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000049232.

HOVERGEN

HBG007316.

InParanoid

Q02763.

KO

K05121.

OMA

VDIFAEN.

OrthoDB

EOG47H5P6.

PhylomeDB

Q02763.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.

Reactome

REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

Q02763.

Bgee

Q02763.

CleanEx

HS_TEK.

Genevestigator

Q02763.

GermOnline

ENSG00000120156. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 6 hits.

InterPro

IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
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. 2 hits.
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

Q02763.

ChEMBL

CHEMBL4128.

ChiTaRS

TEK. human.

EvolutionaryTrace

Q02763.

GenomeRNAi

7010.

NextBio

27384.

SOURCE

Search...

Entry information

Entry name

TIE2_HUMAN

Accession

Primary (citable) accession number: Q02763
Secondary accession number(s): A8K6W0 , B4DH20, B4DHD3, D3DRK5, E7EWI2, Q5TCU2, Q8IV34

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	December 16, 2008
Last modified:	May 1, 2013
This is version 152 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.