P35968 (VGFR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vascular endothelial growth factor receptor 2
Short name=VEGFR-2
EC=2.7.10.1

Alternative name(s):
Fetal liver kinase 1
Short name=FLK-1
Kinase insert domain receptor
Short name=KDR
Protein-tyrosine kinase receptor flk-1
CD_antigen=CD309

Gene names

Name:	KDR
Synonyms:	FLK1, VEGFR2

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	1356 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 a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. Ref.2 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.18 Ref.19 Ref.21 Ref.23 Ref.24 Ref.25 Ref.27 Ref.30 Ref.31 Ref.32 Ref.34 Ref.44 Ref.47 Ref.48
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.15 Ref.16
Enzyme regulation	Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by the small molecule PTK inhibitor SU5614 ((3Z)-5-Chloro-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-2H-indol-2-one). Ref.15 Ref.16 Ref.23
Subunit structure	Interacts with MYOF By similarity. Interacts with VEGFA, VEGFC and VEGFD. Monomer in the absence of bound VEGFA, VEGFC or VEGFD. Homodimer in the presence of bound dimeric VEGFA, VEGFC or VEGFD. Can also form heterodimers with FLT1 and FLT4. Interacts (tyrosine phosphorylated) with FYN, NCK1, PLCG1 and SHB. Interacts with HIV-1 Tat. Interacts with CBL. Interacts with SH2D2A/TSAD and GRB2. Ref.1 Ref.2 Ref.9 Ref.11 Ref.16 Ref.17 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.32 Ref.34 Ref.48 Ref.49
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein. Cytoplasm. Nucleus. Cytoplasmic vesicle. Early endosome. Note: Detected on caveolae-enriched lipid rafts at the cell surface. Is recycled from the plasma membrane to endosomes and back again. Phosphorylation triggered by VEGFA binding promotes internalization and subsequent degradation. VEGFA binding triggers internalization and translocation to the nucleus. Ref.1 Ref.9 Ref.11 Ref.16 Ref.19 Ref.22 Ref.26 Ref.30 Ref.32 Ref.33 Isoform 2: Secreted Probable Ref.1 Ref.9 Ref.11 Ref.16 Ref.19 Ref.22 Ref.26 Ref.30 Ref.32 Ref.33. Isoform 3: Secreted Ref.1 Ref.9 Ref.11 Ref.16 Ref.19 Ref.22 Ref.26 Ref.30 Ref.32 Ref.33.
Tissue specificity	Detected in cornea (at protein level). Widely expressed. Ref.2
Domain	The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding. Ref.49
Post-translational modification	N-glycosylated. Ref.11 Ref.49 Ref.50 Ubiquitinated. Tyrosine phosphorylation of the receptor promotes its poly-ubiquitination, leading to its degradation via the proteasome or lysosomal proteases. Ref.19 Ref.26 Ref.30 Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-951 is important for interaction with SH2D2A/TSAD and VEGFA-mediated reorganization of the actin cytoskeleton. Phosphorylation at Tyr-1175 is important for interaction with PLCG1 and SHB. Phosphorylation at Tyr-1214 is important for interaction with NCK1 and FYN. Dephosphorylated by PTPRB. Dephosphorylated by PTPRJ at Tyr-951, Tyr-996, Tyr-1054, Tyr-1059, Tyr-1175 and Tyr-1214. Ref.10 Ref.11 Ref.15 Ref.16 Ref.18 Ref.22 Ref.23 Ref.24 Ref.27 Ref.28 Ref.29 Ref.44 Ref.48
Involvement in disease	Hemangioma, capillary infantile (HCI) [MIM:602089]: A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.51 Ref.54 Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. Contains 7 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Angiogenesis Differentiation Host-virus interaction
Cellular component	Cell membrane Cytoplasm Cytoplasmic vesicle Endosome Membrane Nucleus Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	branching morphogenesis of an epithelial tube Inferred from electronic annotation. Source: Compara calcium ion homeostasis Inferred from electronic annotation. Source: Compara calcium-mediated signaling using intracellular calcium source Inferred from mutant phenotype Ref.23. Source: UniProtKB cell fate commitment Inferred from electronic annotation. Source: Compara cell maturation Inferred from electronic annotation. Source: Compara cell migration involved in sprouting angiogenesis Inferred from sequence or structural similarity. Source: BHF-UCL embryonic hemopoiesis Inferred from sequence or structural similarity. Source: UniProtKB endothelial cell differentiation Inferred from electronic annotation. Source: Compara endothelium development Inferred from sequence or structural similarity. Source: UniProtKB lung alveolus development Inferred from electronic annotation. Source: Compara lymph vessel development Inferred from electronic annotation. Source: Compara negative regulation of endothelial cell apoptotic process Inferred from direct assay Ref.13. Source: UniProtKB ovarian follicle development Inferred from electronic annotation. Source: Compara peptidyl-tyrosine autophosphorylation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of ERK1 and ERK2 cascade Inferred from mutant phenotype Ref.23. Source: UniProtKB positive regulation of angiogenesis Inferred from mutant phenotype Ref.23. Source: UniProtKB positive regulation of endothelial cell migration Inferred from mutant phenotype PubMed 10022831. Source: BHF-UCL positive regulation of endothelial cell proliferation Inferred from mutant phenotype Ref.18. Source: UniProtKB positive regulation of focal adhesion assembly Inferred from direct assay PubMed 12820653. Source: BHF-UCL positive regulation of mesenchymal cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of nitric-oxide synthase biosynthetic process Inferred from direct assay Ref.14. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase cascade Inferred from direct assay Ref.13. Source: UniProtKB positive regulation of positive chemotaxis Inferred from direct assay Ref.10. Source: BHF-UCL regulation of cell shape Inferred from direct assay Ref.10. Source: BHF-UCL surfactant homeostasis Inferred from electronic annotation. Source: Compara vascular endothelial growth factor receptor signaling pathway Inferred from direct assay Ref.16Ref.18Ref.23. Source: UniProtKB vasculogenesis Inferred from sequence or structural similarity. Source: UniProtKB virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi apparatus Inferred from direct assay PubMed 23262137. Source: UniProtKB cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell early endosome Inferred from sequence or structural similarity. Source: BHF-UCL external side of plasma membrane Inferred from electronic annotation. Source: Compara extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Inferred from direct assay Ref.16. Source: UniProtKB membrane raft Inferred from direct assay PubMed 23262137. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW Hsp90 protein binding Traceable author statement PubMed 19267251. Source: BHF-UCL receptor signaling protein tyrosine kinase activity Traceable author statement PubMed 10022831. Source: BHF-UCL vascular endothelial growth factor-activated receptor activity Inferred from direct assay Ref.16Ref.18Ref.23. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FLT4	P35916	3	EBI-1005487,EBI-1005467
MET	P08581	3	EBI-1005487,EBI-1039152
SRC	P12931	2	EBI-1005487,EBI-621482
VEGFA	P15692-4	2	EBI-1005487,EBI-1026691

Alternative products

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

Isoform 1 (identifier: P35968-1)

Also known as: mbVegfr-2;

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: P35968-2)

Also known as: sVegfr-2;

The sequence of this isoform differs from the canonical sequence as follows:
     663-678: ERVAPTITGNLENQTT → GRETILDHCAEAVGMP
     679-1356: Missing.

Isoform 3 (identifier: P35968-3)

Also known as: VEGFR2-712;

The sequence of this isoform differs from the canonical sequence as follows:
     712-712: G → E
     713-1356: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Potential

Chain

20 – 1356

1337

Vascular endothelial growth factor receptor 2

PRO_0000016771

Regions

Topological domain

20 – 764

745

Extracellular Potential

Transmembrane

765 – 785

21

Helical; Potential

Topological domain

786 – 1356

571

Cytoplasmic Potential

Domain

46 – 110

65

Ig-like C2-type 1

Domain

141 – 207

67

Ig-like C2-type 2

Domain

224 – 320

97

Ig-like C2-type 3

Domain

328 – 414

87

Ig-like C2-type 4

Domain

421 – 548

128

Ig-like C2-type 5

Domain

551 – 660

110

Ig-like C2-type 6

Domain

667 – 753

87

Ig-like C2-type 7

Domain

834 – 1162

329

Protein kinase

Nucleotide binding

840 – 848

9

ATP Probable

Sites

Active site

1028

1

Proton acceptor By similarity

Binding site

868

1

ATP Probable

Site

1175

1

Interaction with SHB By similarity

Amino acid modifications

Modified residue

801

1

Phosphotyrosine Ref.27 Ref.29

Modified residue

951

1

Phosphotyrosine; by autocatalysis Ref.24 Ref.28 Ref.29

Modified residue

982

1

Phosphoserine Ref.43

Modified residue

984

1

Phosphoserine Ref.43

Modified residue

996

1

Phosphotyrosine; by autocatalysis Ref.16 Ref.29

Modified residue

1054

1

Phosphotyrosine; by autocatalysis Ref.15 Ref.16 Ref.23 Ref.24 Ref.29

Modified residue

1059

1

Phosphotyrosine; by autocatalysis Ref.15 Ref.16 Ref.23 Ref.24 Ref.29 Ref.44

Modified residue

1175

1

Phosphotyrosine; by autocatalysis Ref.18 Ref.28 Ref.29

Modified residue

1214

1

Phosphotyrosine; by autocatalysis Ref.18 Ref.24 Ref.28 Ref.29

Modified residue

1305

1

Phosphotyrosine; by autocatalysis Ref.24

Modified residue

1309

1

Phosphotyrosine; by autocatalysis Ref.24

Modified residue

1319

1

Phosphotyrosine; by autocatalysis Ref.24

Glycosylation

46

1

N-linked (GlcNAc...) Potential

Glycosylation

66

1

N-linked (GlcNAc...) Potential

Glycosylation

96

1

N-linked (GlcNAc...) Potential

Glycosylation

143

1

N-linked (GlcNAc...) Ref.49

Glycosylation

158

1

N-linked (GlcNAc...) Potential

Glycosylation

245

1

N-linked (GlcNAc...) Ref.49 Ref.50

Glycosylation

318

1

N-linked (GlcNAc...) Ref.49 Ref.50

Glycosylation

374

1

N-linked (GlcNAc...) Potential

Glycosylation

395

1

N-linked (GlcNAc...) Potential

Glycosylation

511

1

N-linked (GlcNAc...) Potential

Glycosylation

523

1

N-linked (GlcNAc...) Potential

Glycosylation

580

1

N-linked (GlcNAc...) Potential

Glycosylation

613

1

N-linked (GlcNAc...) Potential

Glycosylation

619

1

N-linked (GlcNAc...) Potential

Glycosylation

631

1

N-linked (GlcNAc...) Potential

Glycosylation

675

1

N-linked (GlcNAc...) Potential

Glycosylation

704

1

N-linked (GlcNAc...) Potential

Glycosylation

721

1

N-linked (GlcNAc...) Potential

Disulfide bond

53 ↔ 103

By similarity

Disulfide bond

150 ↔ 200

Ref.49 Ref.50

Disulfide bond

246 ↔ 307

Ref.49 Ref.50

Disulfide bond

445 ↔ 530

By similarity

Disulfide bond

571 ↔ 642

By similarity

Disulfide bond

688 ↔ 737

By similarity

Natural variations

Alternative sequence

663 – 678

16

ERVAP…ENQTT → GRETILDHCAEAVGMP in isoform 2.

VSP_041988

Alternative sequence

679 – 1356

678

Missing in isoform 2.

VSP_041989

Alternative sequence

712

1

G → E in isoform 3.

VSP_041990

Alternative sequence

713 – 1356

644

Missing in isoform 3.

VSP_041991

Natural variant

2

1

Q → R in a lung adenocarcinoma sample; somatic mutation. Ref.53

VAR_042053

Natural variant

136

1

V → M. Ref.53
Corresponds to variant rs35636987 [ dbSNP | Ensembl ].

VAR_042054

Natural variant

248

1

A → G in a renal clear cell carcinoma sample; somatic mutation. Ref.53

VAR_042055

Natural variant

275

1

R → L in a colorectal cancer sample; somatic mutation. Ref.52

VAR_036126

Natural variant

297

1

V → I. Ref.53
Corresponds to variant rs2305948 [ dbSNP | Ensembl ].

VAR_022071

Natural variant

462

1

L → V. Ref.53
Corresponds to variant rs56286620 [ dbSNP | Ensembl ].

VAR_042056

Natural variant

472

1

Q → H. Ref.6 Ref.53
Corresponds to variant rs1870377 [ dbSNP | Ensembl ].

VAR_020353

Natural variant

482

1

C → R in HCI susceptibility; expression of FLT1 in hemangioma endothelial cells is markedly reduced and KDR activity is increased compared to controls; low FLT1 expression in hemangioma cells is caused by reduced activity of a pathway involving ITGB1, ANTXR1, KDR and NFATC2IP; the mutation predicts to result in loss-of-function and disruption of the normal association of these molecules. Ref.53 Ref.54
Corresponds to variant rs34231037 [ dbSNP | Ensembl ].

VAR_042057

Natural variant

539

1

G → R. Ref.53
Corresponds to variant rs55716939 [ dbSNP | Ensembl ].

VAR_042058

Natural variant

689

1

T → M. Ref.53
Corresponds to variant rs34038364 [ dbSNP | Ensembl ].

VAR_042059

Natural variant

814

1

D → N. Ref.53
Corresponds to variant rs35603373 [ dbSNP | Ensembl ].

VAR_042060

Natural variant

848

1

V → E Strongly reduced autophosphorylation and kinase activity. Ref.7 Ref.15
Corresponds to variant rs1139776 [ dbSNP | Ensembl ].

VAR_046679

Natural variant

873

1

G → R in a colorectal cancer sample; somatic mutation. Ref.52

VAR_036127

Natural variant

952

1

V → I.
Corresponds to variant rs13129474 [ dbSNP | Ensembl ].

VAR_046680

Natural variant

1065

1

A → T. Ref.53
Corresponds to variant rs56302315 [ dbSNP | Ensembl ].

VAR_042061

Natural variant

1147

1

P → S in HCI; somatic mutation. Ref.51

VAR_063147

Experimental info

Mutagenesis

726

1

R → A: Strongly reduced autophosphorylation and activation of MAP kinases. Ref.48

Mutagenesis

731

1

D → A: Strongly reduced autophosphorylation and activation of MAP kinases. Ref.48

Mutagenesis

801

1

Y → F: Abolishes stimulation of nitric oxide synthesis. Ref.27

Mutagenesis

868

1

K → M: Loss of enzyme activity. Ref.18

Mutagenesis

951

1

Y → F: Abolishes reorganization of the actin cytoskeleton and cell migration in response to VEGFA. Ref.24

Mutagenesis

996

1

Y → F: Strongly reduced autophosphorylation. Reduces phosphorylation of PLCG1. Ref.16

Mutagenesis

1054

1

Y → F: Strongly reduced autophosphorylation. Abolishes phosphorylation of downstream signaling proteins; when associated with F-1059. Ref.16

Mutagenesis

1059

1

Y → F: Strongly reduced autophosphorylation. Abolishes phosphorylation of downstream signaling proteins; when associated with F-1054. Ref.16

Mutagenesis

1175

1

Y → F: Abolishes phosphorylation of PLCG1 and MAP kinases in response to VEGFA. Ref.18

Mutagenesis

1214

1

Y → F: Loss of phosphorylation site. Abolishes reorganization of the actin cytoskeleton in response to VEGFA. Ref.25

Sequence conflict

2

1

Q → E in AAC16450. Ref.4

Sequence conflict

772

1

A → T in AAA59459. Ref.7

Sequence conflict

772

1

A → T in CAA43837. Ref.7

Sequence conflict

787

1

R → G in AAA59459. Ref.7

Sequence conflict

787

1

R → G in CAA43837. Ref.7

Sequence conflict

835

1

K → N in AAA59459. Ref.7

Sequence conflict

835

1

K → N in CAA43837. Ref.7

Sequence conflict

1347

1

S → T in AAA59459. Ref.7

Sequence conflict

1347

1

S → T in CAA43837. Ref.7

Secondary structure

1

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1356

Helix Strand Turn

Details...

Beta strand

134 – 138

5

Beta strand

145 – 148

4

Beta strand

152 – 154

3

Beta strand

159 – 164

6

Turn

165 – 167

3

Beta strand

168 – 170

3

Beta strand

174 – 176

3

Beta strand

178 – 180

3

Turn

181 – 183

3

Beta strand

184 – 188

5

Helix

189 – 191

3

Turn

192 – 194

3

Beta strand

196 – 202

7

Beta strand

214 – 218

5

Beta strand

223 – 230

8

Beta strand

234 – 238

5

Beta strand

242 – 250

9

Beta strand

257 – 261

5

Helix

269 – 272

4

Beta strand

279 – 282

4

Beta strand

285 – 296

12

Helix

299 – 301

3

Beta strand

303 – 310

8

Beta strand

315 – 328

14

Beta strand

676 – 679

4

Beta strand

684 – 687

4

Beta strand

697 – 706

10

Beta strand

713 – 716

4

Turn

717 – 720

4

Beta strand

721 – 724

4

Helix

729 – 731

3

Beta strand

733 – 740

8

Beta strand

746 – 755

10

Beta strand

804 – 806

3

Turn

808 – 810

3

Turn

813 – 815

3

Helix

817 – 819

3

Helix

824 – 827

4

Helix

831 – 833

3

Beta strand

834 – 842

9

Beta strand

844 – 858

15

Beta strand

862 – 870

9

Helix

876 – 892

17

Beta strand

901 – 905

5

Beta strand

907 – 910

4

Beta strand

913 – 917

5

Helix

924 – 929

6

Turn

930 – 933

4

Beta strand

934 – 936

3

Turn

995 – 998

4

Helix

1002 – 1021

20

Beta strand

1024 – 1026

3

Helix

1031 – 1033

3

Beta strand

1034 – 1036

3

Helix

1038 – 1040

3

Beta strand

1042 – 1044

3

Helix

1048 – 1050

3

Turn

1053 – 1055

3

Beta strand

1059 – 1062

4

Beta strand

1065 – 1067

3

Helix

1069 – 1071

3

Helix

1074 – 1079

6

Helix

1084 – 1099

16

Beta strand

1105 – 1108

4

Helix

1113 – 1121

9

Helix

1133 – 1142

10

Helix

1147 – 1149

3

Helix

1153 – 1167

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (mbVegfr-2) [UniParc]. Last modified December 1, 2000. Version 2. Checksum: 59E7C44B05CFEBB3	FASTA	1,356	151,527
	10 20 30 40 50 60 MQSKVLLAVA LWLCVETRAA SVGLPSVSLD LPRLSIQKDI LTIKANTTLQ ITCRGQRDLD 70 80 90 100 110 120 WLWPNNQSGS EQRVEVTECS DGLFCKTLTI PKVIGNDTGA YKCFYRETDL ASVIYVYVQD 130 140 150 160 170 180 YRSPFIASVS DQHGVVYITE NKNKTVVIPC LGSISNLNVS LCARYPEKRF VPDGNRISWD 190 200 210 220 230 240 SKKGFTIPSY MISYAGMVFC EAKINDESYQ SIMYIVVVVG YRIYDVVLSP SHGIELSVGE 250 260 270 280 290 300 KLVLNCTART ELNVGIDFNW EYPSSKHQHK KLVNRDLKTQ SGSEMKKFLS TLTIDGVTRS 310 320 330 340 350 360 DQGLYTCAAS SGLMTKKNST FVRVHEKPFV AFGSGMESLV EATVGERVRI PAKYLGYPPP 370 380 390 400 410 420 EIKWYKNGIP LESNHTIKAG HVLTIMEVSE RDTGNYTVIL TNPISKEKQS HVVSLVVYVP 430 440 450 460 470 480 PQIGEKSLIS PVDSYQYGTT QTLTCTVYAI PPPHHIHWYW QLEEECANEP SQAVSVTNPY 490 500 510 520 530 540 PCEEWRSVED FQGGNKIEVN KNQFALIEGK NKTVSTLVIQ AANVSALYKC EAVNKVGRGE 550 560 570 580 590 600 RVISFHVTRG PEITLQPDMQ PTEQESVSLW CTADRSTFEN LTWYKLGPQP LPIHVGELPT 610 620 630 640 650 660 PVCKNLDTLW KLNATMFSNS TNDILIMELK NASLQDQGDY VCLAQDRKTK KRHCVVRQLT 670 680 690 700 710 720 VLERVAPTIT GNLENQTTSI GESIEVSCTA SGNPPPQIMW FKDNETLVED SGIVLKDGNR 730 740 750 760 770 780 NLTIRRVRKE DEGLYTCQAC SVLGCAKVEA FFIIEGAQEK TNLEIIILVG TAVIAMFFWL 790 800 810 820 830 840 LLVIILRTVK RANGGELKTG YLSIVMDPDE LPLDEHCERL PYDASKWEFP RDRLKLGKPL 850 860 870 880 890 900 GRGAFGQVIE ADAFGIDKTA TCRTVAVKML KEGATHSEHR ALMSELKILI HIGHHLNVVN 910 920 930 940 950 960 LLGACTKPGG PLMVIVEFCK FGNLSTYLRS KRNEFVPYKT KGARFRQGKD YVGAIPVDLK 970 980 990 1000 1010 1020 RRLDSITSSQ SSASSGFVEE KSLSDVEEEE APEDLYKDFL TLEHLICYSF QVAKGMEFLA 1030 1040 1050 1060 1070 1080 SRKCIHRDLA ARNILLSEKN VVKICDFGLA RDIYKDPDYV RKGDARLPLK WMAPETIFDR 1090 1100 1110 1120 1130 1140 VYTIQSDVWS FGVLLWEIFS LGASPYPGVK IDEEFCRRLK EGTRMRAPDY TTPEMYQTML 1150 1160 1170 1180 1190 1200 DCWHGEPSQR PTFSELVEHL GNLLQANAQQ DGKDYIVLPI SETLSMEEDS GLSLPTSPVS 1210 1220 1230 1240 1250 1260 CMEEEEVCDP KFHYDNTAGI SQYLQNSKRK SRPVSVKTFE DIPLEEPEVK VIPDDNQTDS 1270 1280 1290 1300 1310 1320 GMVLASEELK TLEDRTKLSP SFGGMVPSKS RESVASEGSN QTSGYQSGYH SDDTDTTVYS 1330 1340 1350 SEEAELLKLI EIGVQTGSTA QILQPDSGTT LSSPPV
	Isoform 2 (sVegfr-2) [UniParc]. Checksum: BD4BD2686CE95EB9	FASTA	678	75,896
	10 20 30 40 50 60 MQSKVLLAVA LWLCVETRAA SVGLPSVSLD LPRLSIQKDI LTIKANTTLQ ITCRGQRDLD 70 80 90 100 110 120 WLWPNNQSGS EQRVEVTECS DGLFCKTLTI PKVIGNDTGA YKCFYRETDL ASVIYVYVQD 130 140 150 160 170 180 YRSPFIASVS DQHGVVYITE NKNKTVVIPC LGSISNLNVS LCARYPEKRF VPDGNRISWD 190 200 210 220 230 240 SKKGFTIPSY MISYAGMVFC EAKINDESYQ SIMYIVVVVG YRIYDVVLSP SHGIELSVGE 250 260 270 280 290 300 KLVLNCTART ELNVGIDFNW EYPSSKHQHK KLVNRDLKTQ SGSEMKKFLS TLTIDGVTRS 310 320 330 340 350 360 DQGLYTCAAS SGLMTKKNST FVRVHEKPFV AFGSGMESLV EATVGERVRI PAKYLGYPPP 370 380 390 400 410 420 EIKWYKNGIP LESNHTIKAG HVLTIMEVSE RDTGNYTVIL TNPISKEKQS HVVSLVVYVP 430 440 450 460 470 480 PQIGEKSLIS PVDSYQYGTT QTLTCTVYAI PPPHHIHWYW QLEEECANEP SQAVSVTNPY 490 500 510 520 530 540 PCEEWRSVED FQGGNKIEVN KNQFALIEGK NKTVSTLVIQ AANVSALYKC EAVNKVGRGE 550 560 570 580 590 600 RVISFHVTRG PEITLQPDMQ PTEQESVSLW CTADRSTFEN LTWYKLGPQP LPIHVGELPT 610 620 630 640 650 660 PVCKNLDTLW KLNATMFSNS TNDILIMELK NASLQDQGDY VCLAQDRKTK KRHCVVRQLT 670 VLGRETILDH CAEAVGMP
	Isoform 3 (VEGFR2-712) [UniParc]. Checksum: 1043A452AE64A528	FASTA	712	79,634
	10 20 30 40 50 60 MQSKVLLAVA LWLCVETRAA SVGLPSVSLD LPRLSIQKDI LTIKANTTLQ ITCRGQRDLD 70 80 90 100 110 120 WLWPNNQSGS EQRVEVTECS DGLFCKTLTI PKVIGNDTGA YKCFYRETDL ASVIYVYVQD 130 140 150 160 170 180 YRSPFIASVS DQHGVVYITE NKNKTVVIPC LGSISNLNVS LCARYPEKRF VPDGNRISWD 190 200 210 220 230 240 SKKGFTIPSY MISYAGMVFC EAKINDESYQ SIMYIVVVVG YRIYDVVLSP SHGIELSVGE 250 260 270 280 290 300 KLVLNCTART ELNVGIDFNW EYPSSKHQHK KLVNRDLKTQ SGSEMKKFLS TLTIDGVTRS 310 320 330 340 350 360 DQGLYTCAAS SGLMTKKNST FVRVHEKPFV AFGSGMESLV EATVGERVRI PAKYLGYPPP 370 380 390 400 410 420 EIKWYKNGIP LESNHTIKAG HVLTIMEVSE RDTGNYTVIL TNPISKEKQS HVVSLVVYVP 430 440 450 460 470 480 PQIGEKSLIS PVDSYQYGTT QTLTCTVYAI PPPHHIHWYW QLEEECANEP SQAVSVTNPY 490 500 510 520 530 540 PCEEWRSVED FQGGNKIEVN KNQFALIEGK NKTVSTLVIQ AANVSALYKC EAVNKVGRGE 550 560 570 580 590 600 RVISFHVTRG PEITLQPDMQ PTEQESVSLW CTADRSTFEN LTWYKLGPQP LPIHVGELPT 610 620 630 640 650 660 PVCKNLDTLW KLNATMFSNS TNDILIMELK NASLQDQGDY VCLAQDRKTK KRHCVVRQLT 670 680 690 700 710 VLERVAPTIT GNLENQTTSI GESIEVSCTA SGNPPPQIMW FKDNETLVED SE

References

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[2]	"Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth." Albuquerque R.J., Hayashi T., Cho W.G., Kleinman M.E., Dridi S., Takeda A., Baffi J.Z., Yamada K., Kaneko H., Green M.G., Chappell J., Wilting J., Weich H.A., Yamagami S., Amano S., Mizuki N., Alexander J.S., Peterson M.L. , Brekken R.A., Hirashima M., Capoor S., Usui T., Ambati B.K., Ambati J. Nat. Med. 15:1023-1030(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION IN INHIBITION OF LYMPHANGIOGENESIS, INTERACTION WITH VEGFC, TISSUE SPECIFICITY.
[3]	"Full length human KDR/flk-1 sequence." Yin L.Y., Wu Y., Patterson C. Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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[6]	"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 HIS-472.
[7]	"Identification of a new endothelial cell growth factor receptor tyrosine kinase." Terman B.I., Carrion M.E., Kovacs E., Rasmussen B.A., Eddy R.L., Shows T.B. Oncogene 6:1677-1683(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-1356 (ISOFORM 1), VARIANT GLU-848. Tissue: Umbilical vein.
[8]	"Cloning and functional analysis of the promoter for KDR/flk-1, a receptor for vascular endothelial growth factor." Patterson C., Perrella M.A., Hsieh C.-M., Yoshizumi M., Lee M.-E., Harber E. J. Biol. Chem. 270:23111-23118(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
[9]	"Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor." Terman B.I., Dougher-Vermazen M., Carrion M.E., Dimitrov D., Armellino D.C., Gospodarowicz D., Boehlen P. Biochem. Biophys. Res. Commun. 187:1579-1586(1992) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH VEGFA.
[10]	"Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor." Waltenberger J., Claesson-Welsh L., Siegbahn A., Shibuya M., Heldin C.H. J. Biol. Chem. 269:26988-26995(1994) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS VEGFA RECEPTOR; IN REGULATION OF CELL SHAPE; ACTIN CYTOSKELETON REORGANIZATION; CELL MIGRATION AND CELL PROLIFERATION, AUTOPHOSPHORYLATION.
[11]	"The 230 kDa mature form of KDR/Flk-1 (VEGF receptor-2) activates the PLC-gamma pathway and partially induces mitotic signals in NIH3T3 fibroblasts." Takahashi T., Shibuya M. Oncogene 14:2079-2089(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN VEGFA SIGNALING; PHOSPHORYLATION OF PLCG1; ACTIVATION OF MAP KINASES AND IN PROMOTING PROLIFERATION OF ENDOTHELIAL CELLS, INTERACTION WITH VEGFA AND PLCG1, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, GLYCOSYLATION.
[12]	"VEGF-A induces expression of eNOS and iNOS in endothelial cells via VEGF receptor-2 (KDR)." Kroll J., Waltenberger J. Biochem. Biophys. Res. Commun. 252:743-746(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN INDUCTION OF NOS2 AND NOS3.
[13]	"Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation." Gerber H.P., McMurtrey A., Kowalski J., Yan M., Keyt B.A., Dixit V., Ferrara N. J. Biol. Chem. 273:30336-30343(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION OF THE PHOSPHATIDYLINOSITOL 3-KINASE AND AKT1 SIGNALING PATHWAY.
[14]	"A novel function of VEGF receptor-2 (KDR): rapid release of nitric oxide in response to VEGF-A stimulation in endothelial cells." Kroll J., Waltenberger J. Biochem. Biophys. Res. Commun. 265:636-639(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN NITRIC OXIDE RELEASE.
[15]	"Vascular endothelial growth factor receptor KDR tyrosine kinase activity is increased by autophosphorylation of two activation loop tyrosine residues." Kendall R.L., Rutledge R.Z., Mao X., Tebben A.J., Hungate R.W., Thomas K.A. J. Biol. Chem. 274:6453-6460(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANT GLU-848, PHOSPHORYLATION AT TYR-1054 AND TYR-1059, ENZYME REGULATION.
[16]	"Autophosphorylation of KDR in the kinase domain is required for maximal VEGF-stimulated kinase activity and receptor internalization." Dougher M., Terman B.I. Oncogene 18:1619-1627(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF PLCG1 AND PTK2/FAK1, INTERACTION WITH VEGFA, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-996; TYR-1054 AND TYR-1059, MUTAGENESIS OF TYR-996; TYR-1054 AND TYR-1059, SUBCELLULAR LOCATION, ENZYME REGULATION.
[17]	"Identification of specific molecular structures of human immunodeficiency virus type 1 Tat relevant for its biological effects on vascular endothelial cells." Mitola S., Soldi R., Zanon I., Barra L., Gutierrez M.I., Berkhout B., Giacca M., Bussolino F. J. Virol. 74:344-353(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIV-1 TAT.
[18]	"A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells." Takahashi T., Yamaguchi S., Chida K., Shibuya M. EMBO J. 20:2768-2778(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ENDOTHELIAL CELL PROLIFERATION; PHOSPHORYLATION OF PLCG1 AND ACTIVATION OF MAP KINASES, PHOSPHORYLATION AT TYR-1175 AND TYR-1214, MUTAGENESIS OF LYS-868 AND TYR-1175.
[19]	"Vascular endothelial growth factor-dependent down-regulation of Flk-1/KDR involves Cbl-mediated ubiquitination. Consequences on nitric oxide production from endothelial cells." Duval M., Bedard-Goulet S., Delisle C., Gratton J.P. J. Biol. Chem. 278:20091-20097(2003) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, FUNCTION IN NITRIC OXIDE PRODUCTION, SUBCELLULAR LOCATION, INTERACTION WITH CBL.
[20]	"Ligand-induced vascular endothelial growth factor receptor-3 (VEGFR-3) heterodimerization with VEGFR-2 in primary lymphatic endothelial cells regulates tyrosine phosphorylation sites." Dixelius J., Makinen T., Wirzenius M., Karkkainen M.J., Wernstedt C., Alitalo K., Claesson-Welsh L. J. Biol. Chem. 278:40973-40979(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FLT4.
[21]	"The adaptor protein shb binds to tyrosine 1175 in vascular endothelial growth factor (VEGF) receptor-2 and regulates VEGF-dependent cellular migration." Holmqvist K., Cross M.J., Rolny C., Haegerkvist R., Rahimi N., Matsumoto T., Claesson-Welsh L., Welsh M. J. Biol. Chem. 279:22267-22275(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SHB, FUNCTION IN CELL MIGRATION.
[22]	"Phosphorylated KDR is expressed in the neoplastic and stromal elements of human renal tumours and shuttles from cell membrane to nucleus." Fox S.B., Turley H., Cheale M., Blazquez C., Roberts H., James N., Cook N., Harris A., Gatter K. J. Pathol. 202:313-320(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION.
[23]	"Vascular endothelial growth factor (VEGF)-D and VEGF-A differentially regulate KDR-mediated signaling and biological function in vascular endothelial cells." Jia H., Bagherzadeh A., Bicknell R., Duchen M.R., Liu D., Zachary I. J. Biol. Chem. 279:36148-36157(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VEGFA AND VEGFD, PHOSPHORYLATION AT TYR-1054 AND TYR-1059, FUNCTION IN VEGFA AND VEGFD SIGNALING; ACTIVATION OF MAPK1/ERK2 AND MAPK3/ERK1; ACTIVATION OF AKT1; PHOSPHORYLATION OF PLCG1 AND NOS3; MODULATION OF INTRACELLULAR CA(2+) LEVELS; CELL SURVIVAL AND POSITIVE REGULATION OF CELL PROLIFERATION; CELL MIGRATION AND ANGIOGENESIS, ENZYME REGULATION.
[24]	"VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis." Matsumoto T., Bohman S., Dixelius J., Berge T., Dimberg A., Magnusson P., Wang L., Wikner C., Qi J.H., Wernstedt C., Wu J., Bruheim S., Mugishima H., Mukhopadhyay D., Spurkland A., Claesson-Welsh L. EMBO J. 24:2342-2353(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL MIGRATION; PHOSPHORYLATION OF PLCG1; ACTIVATION OF MAPK1/ERK2; MAPK3/ERK1 AND THE MAP KINASES AND IN REGULATION OF ACTIN CYTOSKELETON REORGANIZATION, INTERACTION WITH SH2D2A/TSAD, PHOSPHORYLATION AT TYR-951; TYR-1054; TYR-1059; TYR-1214; TYR-1305; TYR-1309 AND TYR-1319, MUTAGENESIS OF TYR-951.
[25]	"Phosphorylation of Tyr1214 within VEGFR-2 triggers the recruitment of Nck and activation of Fyn leading to SAPK2/p38 activation and endothelial cell migration in response to VEGF." Lamalice L., Houle F., Huot J. J. Biol. Chem. 281:34009-34020(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ENDOTHELIAL CELL MIGRATION; ACTIVATION OF MAP KINASES AND IN PHOSPHORYLATION OF FYN; SRC AND NCK1, INTERACTION WITH GRB2; FYN AND NCK1, MUTAGENESIS OF TYR-1214.
[26]	"Intrinsic tyrosine kinase activity is required for vascular endothelial growth factor receptor 2 ubiquitination, sorting and degradation in endothelial cells." Ewan L.C., Jopling H.M., Jia H., Mittar S., Bagherzadeh A., Howell G.J., Walker J.H., Zachary I.C., Ponnambalam S. Traffic 7:1270-1282(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, UBIQUITINATION, DEGRADATION.
[27]	"Phosphorylation of tyrosine 801 of vascular endothelial growth factor receptor-2 is necessary for Akt-dependent endothelial nitric-oxide synthase activation and nitric oxide release from endothelial cells." Blanes M.G., Oubaha M., Rautureau Y., Gratton J.P. J. Biol. Chem. 282:10660-10669(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION OF AKT1; PHOSPHORYLATION OF PLCG1 AND NOS3 AND REGULATION OF NITRIC OXIDE PRODUCTION, PHOSPHORYLATION AT TYR-801, MUTAGENESIS OF TYR-801.
[28]	"Transcriptional profiling reveals a critical role for tyrosine phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial cell morphogenesis." Mellberg S., Dimberg A., Bahram F., Hayashi M., Rennel E., Ameur A., Westholm J.O., Larsson E., Lindahl P., Cross M.J., Claesson-Welsh L. FASEB J. 23:1490-1502(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-951; TYR-1175 AND TYR-1214, DEPHOSPHORYLATION BY PTPRB.
[29]	"New role for the protein tyrosine phosphatase DEP-1 in Akt activation and endothelial cell survival." Chabot C., Spring K., Gratton J.P., Elchebly M., Royal I. Mol. Cell. Biol. 29:241-253(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-801; TYR-951; TYR-996; TYR-1054; TYR-1059; TYR-1175 AND TYR-1214; DEPHOSPHORYLATION BY PTPRJ AT TYR-951; TYR-996; TYR-1054; TYR-1059; TYR-1175 AND TYR-1214.
[30]	"VEGF-dependent tumor angiogenesis requires inverse and reciprocal regulation of VEGFR1 and VEGFR2." Zhang Z., Neiva K.G., Lingen M.W., Ellis L.M., Nor J.E. Cell Death Differ. 17:499-512(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS VEGFA RECEPTOR IN TUMOR ANGIOGENESIS, SUBCELLULAR LOCATION, UBIQUITINATION.
[31]	"Neuroblastoma progression correlates with downregulation of the lymphangiogenesis inhibitor sVEGFR-2." Becker J., Pavlakovic H., Ludewig F., Wilting F., Weich H.A., Albuquerque R., Ambati J., Wilting J. Clin. Cancer Res. 16:1431-1441(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN LYMPHANGIOGENESIS (ISOFORM 2).
[32]	"VEGF receptor 2/-3 heterodimers detected in situ by proximity ligation on angiogenic sprouts." Nilsson I., Bahram F., Li X., Gualandi L., Koch S., Jarvius M., Soderberg O., Anisimov A., Kholova I., Pytowski B., Baldwin M., Yla-Herttuala S., Alitalo K., Kreuger J., Claesson-Welsh L. EMBO J. 29:1377-1388(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VEGFC AND FLT4, SUBCELLULAR LOCATION, FUNCTION IN ANGIOGENESIS.
[33]	"The VEGFR2 receptor tyrosine kinase undergoes constitutive endosome-to-plasma membrane recycling." Jopling H.M., Howell G.J., Gamper N., Ponnambalam S. Biochem. Biophys. Res. Commun. 410:170-176(2011) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[34]	"Blood vessel endothelial VEGFR-2 delays lymphangiogenesis: an endogenous trapping mechanism links lymph- and angiogenesis." Nakao S., Zandi S., Hata Y., Kawahara S., Arita R., Schering A., Sun D., Melhorn M.I., Ito Y., Lara-Castillo N., Ishibashi T., Hafezi-Moghadam A. Blood 117:1081-1090(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN LYMPHANGIOGENESIS, INTERACTION WITH FLT4 AND VEGFC.
[35]	"Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesis." Shibuya M. J. Biochem. Mol. Biol. 39:469-478(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ROLE IN ANGIOGENESIS.
[36]	"Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition." Holmes K., Roberts O.L., Thomas A.M., Cross M.J. Cell. Signal. 19:2003-2012(2007) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[37]	"VEGF receptor protein-tyrosine kinases: structure and regulation." Roskoski R. Jr. Biochem. Biophys. Res. Commun. 375:287-291(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON STRUCTURE AND FUNCTION.
[38]	"VEGFs and receptors involved in angiogenesis versus lymphangiogenesis." Lohela M., Bry M., Tammela T., Alitalo K. Curr. Opin. Cell Biol. 21:154-165(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ROLE IN ANGIOGENESIS AND CANCER.
[39]	"Structure-function analysis of VEGF receptor activation and the role of coreceptors in angiogenic signaling." Grunewald F.S., Prota A.E., Giese A., Ballmer-Hofer K. Biochim. Biophys. Acta 1804:567-580(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON LIGAND SPECIFICITY; FUNCTION; STRUCTURE; PHOSPHORYLATION AND SIGNALING.
[40]	"Vascular endothelial growth factor receptor-2 in breast cancer." Guo S., Colbert L.S., Fuller M., Zhang Y., Gonzalez-Perez R.R. Biochim. Biophys. Acta 1806:108-121(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ROLE IN ANGIOGENESIS AND CANCER.
[41]	"Tyrosine kinase receptor Flt/VEGFR family: its characterization related to angiogenesis and cancer." Shibuya M. Genes Cancer 1:1119-1123(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ROLE IN ANGIOGENESIS AND CANCER.
[42]	"Signal transduction by vascular endothelial growth factor receptors." Koch S., Tugues S., Li X., Gualandi L., Claesson-Welsh L. Biochem. J. 437:169-183(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON LIGAND SPECIFICITY; FUNCTION; STRUCTURE; PHOSPHORYLATION AND SIGNALING.
[43]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-982 AND SER-984, MASS SPECTROMETRY.
[44]	"Crystal structure of the kinase domain of human vascular endothelial growth factor receptor 2: a key enzyme in angiogenesis." McTigue M.A., Wickersham J.A., Pinko C., Showalter R.E., Parast C.V., Tempczyk-Russell A., Gehring M.R., Mroczkowski B., Kan C.-C., Villafranca J.E., Appelt K. Structure 7:319-330(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 806-1171, FUNCTION, PHOSPHORYLATION AT TYR-1059, MASS SPECTROMETRY.
[45]	"Novel 4-amino-furo[2,3-d]pyrimidines as Tie-2 and VEGFR2 dual inhibitors." Miyazaki Y., Matsunaga S., Tang J., Maeda Y., Nakano M., Philippe R.J., Shibahara M., Liu W., Sato H., Wang L., Nolte R.T. Bioorg. Med. Chem. Lett. 15:2203-2207(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) OF 806-1171 IN COMPLEX WITH SYNTHETIC INHIBITOR.
[46]	"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 (1.95 ANGSTROMS) OF 815-1171 IN COMPLEX WITH SYNTHETIC INHIBITOR.
[47]	"Design, synthesis, and biological evaluation of novel 3-aryl-4-(1H-indole-3yl)-1,5-dihydro-2H-pyrrole-2-ones as vascular endothelial growth factor receptor (VEGF-R) inhibitors." Peifer C., Selig R., Kinkel K., Ott D., Totzke F., Schaechtele C., Heidenreich R., Roecken M., Schollmeyer D., Laufer S. J. Med. Chem. 51:3814-3824(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 806-1171 IN COMPLEX WITH SYNTHETIC INHIBITOR, FUNCTION.
[48]	"Direct contacts between extracellular membrane-proximal domains are required for VEGF receptor activation and cell signaling." Yang Y., Xie P., Opatowsky Y., Schlessinger J. Proc. Natl. Acad. Sci. U.S.A. 107:1906-1911(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 657-764, SUBUNIT, AUTOPHOSPHORYLATION, FUNCTION IN VEGFA SIGNALING AND ACTIVATION OF MAPK1/ERK2 AND MAPK3/ERK1, MUTAGENESIS OF ARG-726 AND ASP-731.
[49]	"Structural determinants of growth factor binding and specificity by VEGF receptor 2." Leppanen V.M., Prota A.E., Jeltsch M., Anisimov A., Kalkkinen N., Strandin T., Lankinen H., Goldman A., Ballmer-Hofer K., Alitalo K. Proc. Natl. Acad. Sci. U.S.A. 107:2425-2430(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 120-326 IN COMPLEX WITH VEGFC, INTERACTION WITH VEGFC, DOMAIN, DISULFIDE BONDS, GLYCOSYLATION AT ASN-143; ASN-245 AND ASN-318.
[50]	"The structural basis for the function of two anti-VEGF receptor 2 antibodies." Franklin M.C., Navarro E.C., Wang Y., Patel S., Singh P., Zhang Y., Persaud K., Bari A., Griffith H., Shen L., Balderes P., Kussie P. Structure 19:1097-1107(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 220-338 IN COMPLEX WITH ANTIBODY FRAGMENT, DISULFIDE BOND, GLYCOSYLATION AT ASN-245 AND ASN-318.
[51]	"Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma." Walter J.W., North P.E., Waner M., Mizeracki A., Blei F., Walker J.W.T., Reinisch J.F., Marchuk D.A. Genes Chromosomes Cancer 33:295-303(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HCI SER-1147.
[52]	"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: VARIANTS [LARGE SCALE ANALYSIS] LEU-275 AND ARG-873.
[53]	"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] ARG-2; MET-136; GLY-248; ILE-297; VAL-462; HIS-472; ARG-482; ARG-539; MET-689; ASN-814 AND THR-1065.
[54]	"Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma." Jinnin M., Medici D., Park L., Limaye N., Liu Y., Boscolo E., Bischoff J., Vikkula M., Boye E., Olsen B.R. Nat. Med. 14:1236-1246(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HCI SUSCEPTIBILITY ARG-482.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

EU826563 mRNA. Translation: ACF47599.1.
FJ899739 mRNA. Translation: ACR78514.1.
AF035121 mRNA. Translation: AAB88005.1.
AF063658 mRNA. Translation: AAC16450.1.
AC021220 Genomic DNA. No translation available.
AC111194 Genomic DNA. No translation available.
BC131822 mRNA. Translation: AAI31823.1.
L04947 mRNA. Translation: AAA59459.1.
X61656 mRNA. Translation: CAA43837.1.
X89776 Genomic DNA. Translation: CAA61916.1.

IPI

IPI00021396.

PIR

JC1402.

RefSeq

NP_002244.1. NM_002253.2.

UniGene

Hs.479756.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1VR2	X-ray	2.40	A	806-1171	[»]
1Y6A	X-ray	2.10	A	806-1171	[»]
1Y6B	X-ray	2.10	A	806-1171	[»]
1YWN	X-ray	1.71	A	806-1171	[»]
2OH4	X-ray	2.05	A	806-1171	[»]
2P2H	X-ray	1.95	A	815-1171	[»]
2P2I	X-ray	2.40	A/B	815-1171	[»]
2QU5	X-ray	2.95	A	815-1171	[»]
2QU6	X-ray	2.10	A/B	815-1171	[»]
2RL5	X-ray	2.65	A	815-1171	[»]
2X1W	X-ray	2.70	L/M/N/O	120-326	[»]
2X1X	X-ray	3.10	R	120-326	[»]
2XIR	X-ray	1.50	A	806-1171	[»]
3B8Q	X-ray	2.75	A/B	815-1171	[»]
3B8R	X-ray	2.70	A/B	815-1171	[»]
3BE2	X-ray	1.75	A	815-1171	[»]
3C7Q	X-ray	2.10	A	806-1171	[»]
3CJF	X-ray	2.15	A	806-1168	[»]
3CJG	X-ray	2.25	A	806-1168	[»]
3CP9	X-ray	2.50	A/B	815-1171	[»]
3CPB	X-ray	2.70	A/B	815-1171	[»]
3CPC	X-ray	2.40	A/B	815-1171	[»]
3DTW	X-ray	2.90	A/B	815-1171	[»]
3EFL	X-ray	2.20	A/B	815-1171	[»]
3EWH	X-ray	1.60	A	815-1171	[»]
3KVQ	X-ray	2.70	A	657-764	[»]
3S35	X-ray	2.20	X	220-338	[»]
3S36	X-ray	3.20	X	220-338	[»]
3S37	X-ray	2.70	X	220-338	[»]
3U6J	X-ray	2.15	A	815-1171	[»]
3VHE	X-ray	1.55	A	811-1169	[»]
3VHK	X-ray	2.49	A	806-1171	[»]
3VID	X-ray	2.30	A	813-1168	[»]
3VNT	X-ray	1.64	A	806-1171	[»]
3VO3	X-ray	1.52	A	806-1171	[»]
4AG8	X-ray	1.95	A	806-1171	[»]
4AGC	X-ray	2.00	A	787-1171	[»]
4AGD	X-ray	2.81	A	787-1171	[»]
4ASD	X-ray	2.03	A	787-1171	[»]
4ASE	X-ray	1.83	A	787-1171	[»]

ProteinModelPortal

P35968.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-486N.

IntAct

P35968. 7 interactions.

MINT

MINT-127732.

STRING

9606.ENSP00000263923.

PTM databases

PhosphoSite

P35968.

Polymorphism databases

DMDM

9087218.

Proteomic databases

PaxDb

P35968.

PRIDE

P35968.

Protocols and materials databases

DNASU

3791.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263923; ENSP00000263923; ENSG00000128052.

GeneID

3791.

KEGG

hsa:3791.

UCSC

uc003has.3. human.

Organism-specific databases

CTD

3791.

GeneCards

GC04M055944.

HGNC

HGNC:6307. KDR.

HPA

CAB004028.

MIM

191306. gene.
602089. phenotype.

neXtProt

NX_P35968.

Orphanet

91415. Familial capillary hemangioma.

PharmGKB

PA30086.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOVERGEN

HBG053432.

InParanoid

P35968.

KO

K05098.

OMA

QDYRSPF.

OrthoDB

EOG48KR9F.

PhylomeDB

P35968.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

avb3_integrin_pathway. Integrins in angiogenesis.
s1p_s1p1_pathway. S1P1 pathway.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P35968.

Bgee

P35968.

CleanEx

HS_KDR.

Genevestigator

P35968.

GermOnline

ENSG00000128052. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 8 hits.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR001824. Tyr_kinase_rcpt_3_CS.
IPR009136. Tyr_kinase_VEGFR2_rcpt.
IPR009134. Tyr_kinase_VEGFR_rcpt_N.
[Graphical view]

Pfam

PF07679. I-set. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]

PRINTS

PR01832. VEGFRECEPTOR.
PR01834. VEGFRECEPTR2.

SMART

SM00409. IG. 4 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS50835. IG_LIKE. 5 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P35968.

ChEMBL

CHEMBL279.

DrugBank

DB00398. Sorafenib.
DB01268. Sunitinib.

EvolutionaryTrace

P35968.

GenomeRNAi

3791.

NextBio

14887.

SOURCE

Search...

Entry information

Entry name

VGFR2_HUMAN

Accession

Primary (citable) accession number: P35968
Secondary accession number(s): A2RRS0 , B5A925, C5IFA0, O60723, Q14178

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	December 1, 2000
Last modified:	May 1, 2013
This is version 154 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.