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P35968 (VGFR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 164. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1356 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.31 Ref.32 Ref.33 Ref.35 Ref.45 Ref.47 Ref.50 Ref.51

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). May be regulated by hydrogen sulfide (H2S) levels via a H2S-sensitive intracellular disulfide bond. Ref.15 Ref.16 Ref.23 Ref.46

Subunit structure

Homodimer in the presence of bound dimeric VEGFA, VEGFC or VEGFD ligands; monomeric in the absence of bound ligands. Can also form heterodimers with FLT1/VEGFR1 and FLT4/VEGFR2. Interacts (tyrosine phosphorylated) with LFYN, NCK1, PLCG1. Interacts (tyrosine-phosphorylated active form preferentially) with DAB2IP (via C2 domain and active form preferentially); the interaction occurs at the late phase of VEGFA response and inhibits KDR/VEGFR2 activity. Interacts with SHBSH2D2A/TSAD, GRB2, MYOF, CBL and PDCD6. Interacts with HIV-1 Tat. 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.28 Ref.33 Ref.35 Ref.45 Ref.51 Ref.52

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.31 Ref.33 Ref.34

Cell junction By similarity. Note: Localized with RAP1A at cell-cell junctions By similarity. Ref.1 Ref.9 Ref.11 Ref.16 Ref.19 Ref.22 Ref.26 Ref.31 Ref.33 Ref.34

Isoform 2: Secreted Probable Ref.1 Ref.9 Ref.11 Ref.16 Ref.19 Ref.22 Ref.26 Ref.31 Ref.33 Ref.34.

Isoform 3: Secreted Ref.1 Ref.9 Ref.11 Ref.16 Ref.19 Ref.22 Ref.26 Ref.31 Ref.33 Ref.34.

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.52

Post-translational modification

N-glycosylated. Ref.11 Ref.52 Ref.53

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.31

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.29 Ref.30 Ref.47 Ref.51

The inhibitory disulfide bond between Cys-1024 and Cys-1045 may serve as a specific molecular switch for H2S-induced modification that regulates VEGFR2 function.

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.54 Ref.57

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 processAngiogenesis
Differentiation
Host-virus interaction
   Cellular componentCell junction
Cell membrane
Cytoplasm
Cytoplasmic vesicle
Endosome
Membrane
Nucleus
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Traceable author statement PubMed 10022831. Source: BHF-UCL

branching morphogenesis of an epithelial tube

Inferred from electronic annotation. Source: Ensembl

calcium ion homeostasis

Inferred from electronic annotation. Source: Ensembl

calcium-mediated signaling using intracellular calcium source

Inferred from mutant phenotype Ref.23. Source: UniProtKB

cell fate commitment

Inferred from electronic annotation. Source: Ensembl

cell maturation

Inferred from electronic annotation. Source: Ensembl

cell migration involved in sprouting angiogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to vascular endothelial growth factor stimulus

Inferred from direct assay Ref.16Ref.18Ref.28. Source: UniProtKB

embryonic hemopoiesis

Inferred from sequence or structural similarity. Source: UniProtKB

endothelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

endothelium development

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular matrix organization

Traceable author statement. Source: Reactome

lung alveolus development

Inferred from electronic annotation. Source: Ensembl

lymph vessel development

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.23. Source: UniProtKB

negative regulation of endothelial cell apoptotic process

Inferred from direct assay Ref.13. Source: UniProtKB

ovarian follicle development

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine autophosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.15Ref.16. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype Ref.23. Source: UniProtKB

positive regulation of MAPK cascade

Inferred from direct assay Ref.18. Source: UniProtKB

positive regulation of angiogenesis

Inferred from mutant phenotype Ref.23. Source: UniProtKB

positive regulation of cell migration

Inferred from mutant phenotype Ref.23. Source: UniProtKB

positive regulation of cell proliferation

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: Ensembl

positive regulation of nitric-oxide synthase biosynthetic process

Inferred from direct assay Ref.14. Source: UniProtKB

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from direct assay Ref.13. Source: UniProtKB

positive regulation of positive chemotaxis

Inferred from direct assay Ref.10. Source: BHF-UCL

positive regulation of protein phosphorylation

Inferred from direct assay Ref.28. Source: UniProtKB

positive regulation of vasculogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.15Ref.16Ref.28. Source: UniProtKB

regulation of cell shape

Inferred from direct assay Ref.10. Source: BHF-UCL

signal transduction by phosphorylation

Traceable author statement PubMed 10022831. Source: GOC

surfactant homeostasis

Inferred from electronic annotation. Source: Ensembl

transmembrane receptor protein tyrosine kinase signaling pathway

Traceable author statement Ref.9. Source: ProtInc

vascular endothelial growth factor receptor signaling pathway

Inferred from direct assay Ref.16Ref.18Ref.23. Source: UniProtKB

vascular endothelial growth factor signaling pathway

Inferred from direct assay PubMed 10022831Ref.16Ref.18Ref.9Ref.23. Source: GOC

vasculogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 23262137. Source: UniProtKB

cell junction

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasmic membrane-bounded vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

early endosome

Inferred from sequence or structural similarity. Source: BHF-UCL

endosome

Inferred from direct assay PubMed 23262137. Source: UniProtKB

external side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of 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

plasma membrane

Inferred from direct assay PubMed 23262137. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Hsp90 protein binding

Traceable author statement PubMed 19267251. Source: BHF-UCL

growth factor binding

Inferred from physical interaction PubMed 10022831Ref.9. Source: BHF-UCL

integrin binding

Inferred from physical interaction PubMed 10022831. Source: BHF-UCL

protein tyrosine kinase activity

Inferred from direct assay Ref.15. Source: UniProtKB

receptor signaling protein tyrosine kinase activity

Traceable author statement PubMed 10022831. Source: BHF-UCL

transmembrane receptor protein tyrosine kinase activity

Traceable author statement Ref.9. Source: BHF-UCL

vascular endothelial growth factor binding

Inferred from physical interaction PubMed 20660291. Source: BHF-UCL

vascular endothelial growth factor-activated receptor activity

Inferred from direct assay Ref.16Ref.18Ref.23. Source: UniProtKB

Complete GO annotation...

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Chain20 – 13561337Vascular endothelial growth factor receptor 2
PRO_0000016771

Regions

Topological domain20 – 764745Extracellular Potential
Transmembrane765 – 78521Helical; Potential
Topological domain786 – 1356571Cytoplasmic Potential
Domain46 – 11065Ig-like C2-type 1
Domain141 – 20767Ig-like C2-type 2
Domain224 – 32097Ig-like C2-type 3
Domain328 – 41487Ig-like C2-type 4
Domain421 – 548128Ig-like C2-type 5
Domain551 – 660110Ig-like C2-type 6
Domain667 – 75387Ig-like C2-type 7
Domain834 – 1162329Protein kinase
Nucleotide binding840 – 8489ATP Probable

Sites

Active site10281Proton acceptor By similarity
Binding site8681ATP Probable
Site11751Interaction with SHB By similarity

Amino acid modifications

Modified residue8011Phosphotyrosine Ref.27 Ref.30
Modified residue9511Phosphotyrosine; by autocatalysis Ref.24 Ref.29 Ref.30
Modified residue9821Phosphoserine Ref.44
Modified residue9841Phosphoserine Ref.44
Modified residue9961Phosphotyrosine; by autocatalysis Ref.16 Ref.30
Modified residue10541Phosphotyrosine; by autocatalysis Ref.15 Ref.16 Ref.23 Ref.24 Ref.30
Modified residue10591Phosphotyrosine; by autocatalysis Ref.15 Ref.16 Ref.23 Ref.24 Ref.30 Ref.47
Modified residue11751Phosphotyrosine; by autocatalysis Ref.18 Ref.29 Ref.30
Modified residue12141Phosphotyrosine; by autocatalysis Ref.18 Ref.24 Ref.29 Ref.30
Modified residue13051Phosphotyrosine; by autocatalysis Ref.24
Modified residue13091Phosphotyrosine; by autocatalysis Ref.24
Modified residue13191Phosphotyrosine; by autocatalysis Ref.24
Glycosylation461N-linked (GlcNAc...) Potential
Glycosylation661N-linked (GlcNAc...) Potential
Glycosylation961N-linked (GlcNAc...) Potential
Glycosylation1431N-linked (GlcNAc...) Ref.52
Glycosylation1581N-linked (GlcNAc...) Potential
Glycosylation2451N-linked (GlcNAc...) Ref.52 Ref.53
Glycosylation3181N-linked (GlcNAc...) Ref.52 Ref.53
Glycosylation3741N-linked (GlcNAc...) Potential
Glycosylation3951N-linked (GlcNAc...) Potential
Glycosylation5111N-linked (GlcNAc...) Potential
Glycosylation5231N-linked (GlcNAc...) Potential
Glycosylation5801N-linked (GlcNAc...) Potential
Glycosylation6131N-linked (GlcNAc...) Potential
Glycosylation6191N-linked (GlcNAc...) Potential
Glycosylation6311N-linked (GlcNAc...) Potential
Glycosylation6751N-linked (GlcNAc...) Potential
Glycosylation7041N-linked (GlcNAc...) Potential
Glycosylation7211N-linked (GlcNAc...) Potential
Disulfide bond53 ↔ 103 By similarity
Disulfide bond150 ↔ 200 Ref.46 Ref.52 Ref.53
Disulfide bond246 ↔ 307 Ref.46 Ref.52 Ref.53
Disulfide bond445 ↔ 530 By similarity
Disulfide bond571 ↔ 642 By similarity
Disulfide bond688 ↔ 737 By similarity
Disulfide bond1024 ↔ 1045Redox-active Ref.46 Ref.52 Ref.53

Natural variations

Alternative sequence663 – 67816ERVAP…ENQTT → GRETILDHCAEAVGMP in isoform 2.
VSP_041988
Alternative sequence679 – 1356678Missing in isoform 2.
VSP_041989
Alternative sequence7121G → E in isoform 3.
VSP_041990
Alternative sequence713 – 1356644Missing in isoform 3.
VSP_041991
Natural variant21Q → R in a lung adenocarcinoma sample; somatic mutation. Ref.56
VAR_042053
Natural variant1361V → M. Ref.56
Corresponds to variant rs35636987 [ dbSNP | Ensembl ].
VAR_042054
Natural variant2481A → G in a renal clear cell carcinoma sample; somatic mutation. Ref.56
VAR_042055
Natural variant2751R → L in a colorectal cancer sample; somatic mutation. Ref.55
VAR_036126
Natural variant2971V → I. Ref.56
Corresponds to variant rs2305948 [ dbSNP | Ensembl ].
VAR_022071
Natural variant4621L → V. Ref.56
Corresponds to variant rs56286620 [ dbSNP | Ensembl ].
VAR_042056
Natural variant4721Q → H. Ref.6 Ref.56
Corresponds to variant rs1870377 [ dbSNP | Ensembl ].
VAR_020353
Natural variant4821C → 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.56 Ref.57
Corresponds to variant rs34231037 [ dbSNP | Ensembl ].
VAR_042057
Natural variant5391G → R. Ref.56
Corresponds to variant rs55716939 [ dbSNP | Ensembl ].
VAR_042058
Natural variant6891T → M. Ref.56
Corresponds to variant rs34038364 [ dbSNP | Ensembl ].
VAR_042059
Natural variant8141D → N. Ref.56
Corresponds to variant rs35603373 [ dbSNP | Ensembl ].
VAR_042060
Natural variant8481V → E Strongly reduced autophosphorylation and kinase activity. Ref.7 Ref.15
Corresponds to variant rs1139776 [ dbSNP | Ensembl ].
VAR_046679
Natural variant8731G → R in a colorectal cancer sample; somatic mutation. Ref.55
VAR_036127
Natural variant9521V → I.
Corresponds to variant rs13129474 [ dbSNP | Ensembl ].
VAR_046680
Natural variant10651A → T. Ref.56
Corresponds to variant rs56302315 [ dbSNP | Ensembl ].
VAR_042061
Natural variant11471P → S in HCI; somatic mutation. Ref.54
VAR_063147

Experimental info

Mutagenesis7261R → A: Strongly reduced autophosphorylation and activation of MAP kinases. Ref.51
Mutagenesis7311D → A: Strongly reduced autophosphorylation and activation of MAP kinases. Ref.51
Mutagenesis8011Y → F: Abolishes stimulation of nitric oxide synthesis. Ref.27
Mutagenesis8681K → M: Loss of enzyme activity. Ref.18
Mutagenesis9511Y → F: Abolishes reorganization of the actin cytoskeleton and cell migration in response to VEGFA. Ref.24
Mutagenesis9961Y → F: Strongly reduced autophosphorylation. Reduces phosphorylation of PLCG1. Ref.16
Mutagenesis10451C → A: Significantly higher kinase activity. Ref.46
Mutagenesis10541Y → F: Strongly reduced autophosphorylation. Abolishes phosphorylation of downstream signaling proteins; when associated with F-1059. Ref.16
Mutagenesis10591Y → F: Strongly reduced autophosphorylation. Abolishes phosphorylation of downstream signaling proteins; when associated with F-1054. Ref.16
Mutagenesis11751Y → F: Abolishes phosphorylation of PLCG1 and MAP kinases in response to VEGFA. Ref.18
Mutagenesis12141Y → F: Loss of phosphorylation site. Abolishes reorganization of the actin cytoskeleton in response to VEGFA. Ref.25
Sequence conflict21Q → E in AAC16450. Ref.4
Sequence conflict7721A → T in AAA59459. Ref.7
Sequence conflict7721A → T in CAA43837. Ref.7
Sequence conflict7871R → G in AAA59459. Ref.7
Sequence conflict7871R → G in CAA43837. Ref.7
Sequence conflict8351K → N in AAA59459. Ref.7
Sequence conflict8351K → N in CAA43837. Ref.7
Sequence conflict13471S → T in AAA59459. Ref.7
Sequence conflict13471S → T in CAA43837. Ref.7

Secondary structure

............................................................................................................................. 1356
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (mbVegfr-2) [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: 59E7C44B05CFEBB3

FASTA1,356151,527
        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 

« Hide

Isoform 2 (sVegfr-2) [UniParc].

Checksum: BD4BD2686CE95EB9
Show »

FASTA67875,896
Isoform 3 (VEGFR2-712) [UniParc].

Checksum: 1043A452AE64A528
Show »

FASTA71279,634

References

« Hide 'large scale' references
[1]"Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis."
Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.
Arthritis Res. Ther. 10:R73-R73(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INTERACTION WITH VEGFC, SUBCELLULAR LOCATION.
[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. expand/collapse author list , 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).
[4]"Coding region for human VEGF receptor KDR (VEGFR-2)."
Yu Y., Whitney R.G., Sato J.D.
Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Umbilical vein.
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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]"AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and inflammatory angiogenesis in mice."
Zhang H., He Y., Dai S., Xu Z., Luo Y., Wan T., Luo D., Jones D., Tang S., Chen H., Sessa W.C., Min W.
J. Clin. Invest. 118:3904-3916(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB2IP.
[29]"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.
[30]"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.
[31]"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.
[32]"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).
[33]"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.
[34]"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.
[35]"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.
[36]"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.
[37]"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.
[38]"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.
[39]"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.
[40]"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.
[41]"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.
[42]"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.
[43]"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.
[44]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[45]"Programmed cell death 6 (PDCD6) inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of VEGFR-2."
Rho S.B., Song Y.J., Lim M.C., Lee S.H., Kim B.R., Park S.Y.
Cell. Signal. 24:131-139(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PDCD6.
[46]"VEGFR2 functions as an H(2)S-targeting receptor protein kinase with its novel Cys1045-Cys1024 disulfide bond serving as a specific molecular switch for hydrogen sulfide actions in vascular endothelial cells."
Tao B.B., Liu S.Y., Zhang C.C., Fu W., Cai W.J., Wang Y., Shen Q., Wang M.J., Chen Y., Zhang L.J., Zhu Y.Z., Zhu Y.C.
Antioxid. Redox Signal. 19:448-464(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, REDOX-ACTIVE DISULFIDE BOND, MUTAGENESIS OF CYS-1045.
[47]"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, IDENTIFICATION BY MASS SPECTROMETRY.
[48]"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.
[49]"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. expand/collapse author list , 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.
[50]"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.
[51]"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.
[52]"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.
[53]"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.
[54]"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.
[55]"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. expand/collapse author list , 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.
[56]"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. expand/collapse author list , 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.
[57]"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.
PIRJC1402.
RefSeqNP_002244.1. NM_002253.2.
UniGeneHs.479756.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1VR2X-ray2.40A806-1171[»]
1Y6AX-ray2.10A806-1171[»]
1Y6BX-ray2.10A806-1171[»]
1YWNX-ray1.71A806-1171[»]
2OH4X-ray2.05A806-1171[»]
2P2HX-ray1.95A815-1171[»]
2P2IX-ray2.40A/B815-1171[»]
2QU5X-ray2.95A815-1171[»]
2QU6X-ray2.10A/B815-1171[»]
2RL5X-ray2.65A815-1171[»]
2X1WX-ray2.70L/M/N/O120-326[»]
2X1XX-ray3.10R120-326[»]
2XIRX-ray1.50A806-1171[»]
3B8QX-ray2.75A/B815-1171[»]
3B8RX-ray2.70A/B815-1171[»]
3BE2X-ray1.75A815-1171[»]
3C7QX-ray2.10A806-1171[»]
3CJFX-ray2.15A806-1168[»]
3CJGX-ray2.25A806-1168[»]
3CP9X-ray2.50A/B815-1171[»]
3CPBX-ray2.70A/B815-1171[»]
3CPCX-ray2.40A/B815-1171[»]
3DTWX-ray2.90A/B815-1171[»]
3EFLX-ray2.20A/B815-1171[»]
3EWHX-ray1.60A815-1171[»]
3KVQX-ray2.70A657-764[»]
3S35X-ray2.20X220-338[»]
3S36X-ray3.20X220-338[»]
3S37X-ray2.70X220-338[»]
3U6JX-ray2.15A815-1171[»]
3V2AX-ray3.20R2-764[»]
3V6BX-ray3.20R132-548[»]
3VHEX-ray1.55A811-1169[»]
3VHKX-ray2.49A806-1171[»]
3VIDX-ray2.30A813-1168[»]
3VNTX-ray1.64A806-1171[»]
3VO3X-ray1.52A806-1171[»]
4AG8X-ray1.95A806-1171[»]
4AGCX-ray2.00A787-1171[»]
4AGDX-ray2.81A787-1171[»]
4ASDX-ray2.03A787-1171[»]
4ASEX-ray1.83A787-1171[»]
ProteinModelPortalP35968.
SMRP35968. Positions 32-756, 815-1209.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109992. 29 interactions.
DIPDIP-486N.
IntActP35968. 20 interactions.
MINTMINT-127732.
STRING9606.ENSP00000263923.

Chemistry

BindingDBP35968.
ChEMBLCHEMBL2111336.
DrugBankDB00398. Sorafenib.
DB01268. Sunitinib.
GuidetoPHARMACOLOGY1813.

PTM databases

PhosphoSiteP35968.

Polymorphism databases

DMDM9087218.

Proteomic databases

PaxDbP35968.
PRIDEP35968.

Protocols and materials databases

DNASU3791.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263923; ENSP00000263923; ENSG00000128052. [P35968-1]
GeneID3791.
KEGGhsa:3791.
UCSCuc003has.3. human. [P35968-1]
uc011bzx.2. human. [P35968-2]

Organism-specific databases

CTD3791.
GeneCardsGC04M055944.
HGNCHGNC:6307. KDR.
HPACAB004028.
MIM191306. gene.
602089. phenotype.
neXtProtNX_P35968.
Orphanet91415. Familial capillary hemangioma.
PharmGKBPA30086.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG053432.
InParanoidP35968.
KOK05098.
OMAAGMVFCE.
OrthoDBEOG75F4CC.
PhylomeDBP35968.
TreeFamTF325768.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_118779. Extracellular matrix organization.
SignaLinkP35968.

Gene expression databases

ArrayExpressP35968.
BgeeP35968.
CleanExHS_KDR.
GenevestigatorP35968.

Family and domain databases

Gene3D2.60.40.10. 8 hits.
InterProIPR007110. 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_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. VEGFR2_rcpt.
[Graphical view]
PANTHERPTHR24416:SF45. PTHR24416:SF45. 1 hit.
PfamPF07679. I-set. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
PRINTSPR01834. VEGFRECEPTR2.
SMARTSM00409. IG. 4 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS50835. 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]
ProtoNetSearch...

Other

EvolutionaryTraceP35968.
GeneWikiKinase_insert_domain_receptor.
GenomeRNAi3791.
NextBio14887.
PROP35968.
SOURCESearch...

Entry information

Entry nameVGFR2_HUMAN
AccessionPrimary (citable) accession number: P35968
Secondary accession number(s): A2RRS0 expand/collapse secondary AC list , B5A925, C5IFA0, O60723, Q14178
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: December 1, 2000
Last modified: April 16, 2014
This is version 164 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries