Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Vascular endothelial growth factor receptor 2

Gene

KDR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Tyrosine-protein kinase that acts as 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.22 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation2 Publications

Enzyme regulationi

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.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei868ATPCurated1
Active sitei1028Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi840 – 848ATPCurated9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • growth factor binding Source: BHF-UCL
  • Hsp90 protein binding Source: BHF-UCL
  • integrin binding Source: BHF-UCL
  • protein tyrosine kinase activity Source: UniProtKB
  • receptor signaling protein tyrosine kinase activity Source: BHF-UCL
  • transmembrane receptor protein tyrosine kinase activity Source: BHF-UCL
  • vascular endothelial growth factor-activated receptor activity Source: UniProtKB
  • vascular endothelial growth factor binding Source: BHF-UCL

GO - Biological processi

  • angiogenesis Source: BHF-UCL
  • calcium-mediated signaling using intracellular calcium source Source: UniProtKB
  • cell migration involved in sprouting angiogenesis Source: BHF-UCL
  • cellular response to vascular endothelial growth factor stimulus Source: UniProtKB
  • embryonic hemopoiesis Source: UniProtKB
  • endothelium development Source: UniProtKB
  • extracellular matrix organization Source: Reactome
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of endothelial cell apoptotic process Source: UniProtKB
  • peptidyl-tyrosine autophosphorylation Source: BHF-UCL
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway Source: BHF-UCL
  • positive regulation of endothelial cell migration Source: BHF-UCL
  • positive regulation of endothelial cell proliferation Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of focal adhesion assembly Source: BHF-UCL
  • positive regulation of macroautophagy Source: MGI
  • positive regulation of MAPK cascade Source: UniProtKB
  • positive regulation of mitochondrial depolarization Source: MGI
  • positive regulation of mitochondrial fission Source: MGI
  • positive regulation of nitric-oxide synthase biosynthetic process Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of positive chemotaxis Source: BHF-UCL
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of vasculogenesis Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • regulation of cell shape Source: BHF-UCL
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: ProtInc
  • vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
  • vasculogenesis Source: UniProtKB
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Angiogenesis, Differentiation, Host-virus interaction

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS05156-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-194306. Neurophilin interactions with VEGF and VEGFR.
R-HSA-195399. VEGF binds to VEGFR leading to receptor dimerization.
R-HSA-216083. Integrin cell surface interactions.
R-HSA-3928663. EPHA-mediated growth cone collapse.
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
R-HSA-5218921. VEGFR2 mediated cell proliferation.
SignaLinkiP35968.
SIGNORiP35968.

Names & Taxonomyi

Protein namesi
Recommended name:
Vascular endothelial growth factor receptor 2 (EC:2.7.10.1)
Short name:
VEGFR-2
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 namesi
Name:KDR
Synonyms:FLK1, VEGFR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:6307. KDR.

Subcellular locationi

Isoform 1 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 764ExtracellularSequence analysisAdd BLAST745
Transmembranei765 – 785HelicalSequence analysisAdd BLAST21
Topological domaini786 – 1356CytoplasmicSequence analysisAdd BLAST571

GO - Cellular componenti

  • cell junction Source: UniProtKB
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • early endosome Source: BHF-UCL
  • endoplasmic reticulum Source: UniProtKB
  • endosome Source: UniProtKB
  • extracellular region Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • membrane raft Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB
  • sorting endosome Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Membrane, Nucleus, Secreted

Pathology & Biotechi

Involvement in diseasei

Hemangioma, capillary infantile (HCI)3 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:602089
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042057482C → R in HCI; associated with disease 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. 2 PublicationsCorresponds to variant rs34231037dbSNPEnsembl.1
Natural variantiVAR_0631471147P → S in HCI; somatic mutation. 1 PublicationCorresponds to variant rs121917766dbSNPEnsembl.1

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.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi726R → A: Strongly reduced autophosphorylation and activation of MAP kinases. 1 Publication1
Mutagenesisi731D → A: Strongly reduced autophosphorylation and activation of MAP kinases. 1 Publication1
Mutagenesisi801Y → F: Abolishes stimulation of nitric oxide synthesis. 1 Publication1
Mutagenesisi868K → M: Loss of enzyme activity. 1 Publication1
Mutagenesisi951Y → F: Abolishes reorganization of the actin cytoskeleton and cell migration in response to VEGFA. 1 Publication1
Mutagenesisi996Y → F: Strongly reduced autophosphorylation. Reduces phosphorylation of PLCG1. 1 Publication1
Mutagenesisi1045C → A: Significantly higher kinase activity. 1 Publication1
Mutagenesisi1054Y → F: Strongly reduced autophosphorylation. Abolishes phosphorylation of downstream signaling proteins; when associated with F-1059. 1 Publication1
Mutagenesisi1059Y → F: Strongly reduced autophosphorylation. Abolishes phosphorylation of downstream signaling proteins; when associated with F-1054. 1 Publication1
Mutagenesisi1175Y → F: Abolishes phosphorylation of PLCG1 and MAP kinases in response to VEGFA. 1 Publication1
Mutagenesisi1214Y → F: Loss of phosphorylation site. Abolishes reorganization of the actin cytoskeleton in response to VEGFA. 1 Publication1

Organism-specific databases

DisGeNETi3791.
MalaCardsiKDR.
MIMi602089. phenotype.
OpenTargetsiENSG00000128052.
Orphaneti91415. Familial capillary hemangioma.
PharmGKBiPA30086.

Chemistry databases

ChEMBLiCHEMBL279.
DrugBankiDB06626. Axitinib.
DB08875. Cabozantinib.
DB09078. Lenvatinib.
DB09079. Nintedanib.
DB06589. Pazopanib.
DB08901. Ponatinib.
DB05578. Ramucirumab.
DB08896. Regorafenib.
DB00398. Sorafenib.
DB01268. Sunitinib.
GuidetoPHARMACOLOGYi1813.

Polymorphism and mutation databases

BioMutaiKDR.
DMDMi9087218.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000001677120 – 1356Vascular endothelial growth factor receptor 2Add BLAST1337

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi46N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi53 ↔ 103PROSITE-ProRule annotation
Glycosylationi66N-linked (GlcNAc...)Sequence analysis1
Glycosylationi96N-linked (GlcNAc...)Sequence analysis1
Glycosylationi143N-linked (GlcNAc...)1 Publication1
Disulfide bondi150 ↔ 200
Glycosylationi158N-linked (GlcNAc...)Sequence analysis1
Glycosylationi245N-linked (GlcNAc...)2 Publications1
Disulfide bondi246 ↔ 307
Glycosylationi318N-linked (GlcNAc...)2 Publications1
Glycosylationi374N-linked (GlcNAc...)Sequence analysis1
Glycosylationi395N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi445 ↔ 530PROSITE-ProRule annotation
Glycosylationi511N-linked (GlcNAc...)Sequence analysis1
Glycosylationi523N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi571 ↔ 642PROSITE-ProRule annotation
Glycosylationi580N-linked (GlcNAc...)Sequence analysis1
Glycosylationi613N-linked (GlcNAc...)Sequence analysis1
Glycosylationi619N-linked (GlcNAc...)Sequence analysis1
Glycosylationi631N-linked (GlcNAc...)Sequence analysis1
Glycosylationi675N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi688 ↔ 737PROSITE-ProRule annotation
Glycosylationi704N-linked (GlcNAc...)Sequence analysis1
Glycosylationi721N-linked (GlcNAc...)Sequence analysis1
Modified residuei801Phosphotyrosine2 Publications1
Modified residuei951Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei982PhosphoserineCombined sources1
Modified residuei984PhosphoserineCombined sources1
Modified residuei996Phosphotyrosine; by autocatalysis2 Publications1
Disulfide bondi1024 ↔ 1045Redox-active
Modified residuei1054Phosphotyrosine; by autocatalysis5 Publications1
Modified residuei1059Phosphotyrosine; by autocatalysis6 Publications1
Modified residuei1175Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei1214Phosphotyrosine; by autocatalysis4 Publications1
Modified residuei1231PhosphoserineBy similarity1
Modified residuei1235PhosphoserineBy similarity1
Modified residuei1238PhosphothreonineBy similarity1
Modified residuei1305Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1309Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1319Phosphotyrosine; by autocatalysis1 Publication1

Post-translational modificationi

N-glycosylated.3 Publications
Ubiquitinated. Tyrosine phosphorylation of the receptor promotes its poly-ubiquitination, leading to its degradation via the proteasome or lysosomal proteases.3 Publications
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-1214.8 Publications
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.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP35968.
MaxQBiP35968.
PaxDbiP35968.
PeptideAtlasiP35968.
PRIDEiP35968.

PTM databases

iPTMnetiP35968.
PhosphoSitePlusiP35968.

Expressioni

Tissue specificityi

Detected in cornea (at protein level). Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000128052.
CleanExiHS_KDR.
ExpressionAtlasiP35968. baseline and differential.
GenevisibleiP35968. HS.

Organism-specific databases

HPAiCAB004028.
HPA030893.

Interactioni

Subunit structurei

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 (PubMed:10102632, PubMed:10590123, PubMed:12649282, PubMed:12881528, PubMed:1417831, PubMed:15026417, PubMed:15215251, PubMed:15837294, PubMed:15962004, PubMed:16966330, PubMed:17253678, PubMed:18529047, PubMed:18593464, PubMed:19033661, PubMed:19668192, PubMed:20080685, PubMed:20145116, PubMed:20224550, PubMed:20705758, PubMed:21827946, PubMed:21893193, PubMed:9160888). Interacts (via C-terminus domain) with ERN1 (via kinase domain); the interaction is facilitated in a XBP1 isoform 1- and vascular endothelial growth factor (VEGF)-dependent manner in endothelial cells (PubMed:23529610).23 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1175Interaction with SHBBy similarity1

Binary interactionsi

WithEntry#Exp.IntActNotes
CRKP461082EBI-1005487,EBI-886
FLT4P359165EBI-1005487,EBI-1005467
GREM1O605654EBI-1005487,EBI-944395
HSPG2P981605EBI-1005487,EBI-947664
ITGA2P173012EBI-1005487,EBI-702960
LGALS1P093823EBI-1005487,EBI-1048875
METP085813EBI-1005487,EBI-1039152
NCK1P163333EBI-1005487,EBI-389883
NRP1O147862EBI-1005487,EBI-1187100
PDCD6O753404EBI-1005487,EBI-352915
PTPRJQ129134EBI-1005487,EBI-2264500
SRCP129312EBI-1005487,EBI-621482
VEGFAP156925EBI-1005487,EBI-1026643
VEGFAP15692-46EBI-1005487,EBI-1026691

GO - Molecular functioni

  • growth factor binding Source: BHF-UCL
  • Hsp90 protein binding Source: BHF-UCL
  • integrin binding Source: BHF-UCL
  • vascular endothelial growth factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi109992. 40 interactors.
DIPiDIP-486N.
IntActiP35968. 33 interactors.
MINTiMINT-127732.
STRINGi9606.ENSP00000263923.

Chemistry databases

BindingDBiP35968.

Structurei

Secondary structure

11356
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi134 – 138Combined sources5
Beta strandi145 – 148Combined sources4
Beta strandi152 – 154Combined sources3
Beta strandi159 – 164Combined sources6
Turni165 – 167Combined sources3
Beta strandi168 – 170Combined sources3
Beta strandi174 – 176Combined sources3
Beta strandi178 – 180Combined sources3
Turni181 – 183Combined sources3
Beta strandi184 – 188Combined sources5
Helixi189 – 191Combined sources3
Turni192 – 194Combined sources3
Beta strandi196 – 202Combined sources7
Beta strandi214 – 218Combined sources5
Beta strandi223 – 230Combined sources8
Beta strandi234 – 238Combined sources5
Beta strandi242 – 250Combined sources9
Beta strandi257 – 261Combined sources5
Helixi269 – 272Combined sources4
Beta strandi279 – 282Combined sources4
Beta strandi285 – 296Combined sources12
Helixi299 – 301Combined sources3
Beta strandi303 – 310Combined sources8
Beta strandi315 – 328Combined sources14
Beta strandi676 – 679Combined sources4
Beta strandi684 – 687Combined sources4
Beta strandi697 – 706Combined sources10
Beta strandi713 – 716Combined sources4
Turni717 – 720Combined sources4
Beta strandi721 – 724Combined sources4
Helixi729 – 731Combined sources3
Beta strandi733 – 740Combined sources8
Beta strandi746 – 755Combined sources10
Helixi760 – 794Combined sources35
Beta strandi804 – 806Combined sources3
Turni808 – 810Combined sources3
Turni813 – 815Combined sources3
Helixi817 – 819Combined sources3
Helixi824 – 827Combined sources4
Helixi831 – 833Combined sources3
Beta strandi834 – 842Combined sources9
Beta strandi844 – 858Combined sources15
Beta strandi862 – 870Combined sources9
Helixi876 – 892Combined sources17
Beta strandi901 – 905Combined sources5
Beta strandi907 – 910Combined sources4
Beta strandi913 – 917Combined sources5
Helixi924 – 929Combined sources6
Turni930 – 933Combined sources4
Beta strandi934 – 936Combined sources3
Turni995 – 998Combined sources4
Helixi1002 – 1021Combined sources20
Beta strandi1024 – 1026Combined sources3
Helixi1031 – 1033Combined sources3
Beta strandi1034 – 1036Combined sources3
Helixi1038 – 1040Combined sources3
Beta strandi1042 – 1044Combined sources3
Helixi1048 – 1050Combined sources3
Turni1053 – 1055Combined sources3
Beta strandi1059 – 1062Combined sources4
Beta strandi1065 – 1067Combined sources3
Helixi1069 – 1071Combined sources3
Helixi1074 – 1079Combined sources6
Helixi1084 – 1099Combined sources16
Beta strandi1105 – 1108Combined sources4
Helixi1113 – 1121Combined sources9
Helixi1133 – 1142Combined sources10
Helixi1147 – 1149Combined sources3
Helixi1153 – 1167Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1VR2X-ray2.40A806-1171[»]
1Y6AX-ray2.10A806-1171[»]
1Y6BX-ray2.10A806-1171[»]
1YWNX-ray1.71A806-1171[»]
2M59NMR-A/B759-795[»]
2METNMR-A/B/C759-795[»]
2MEUNMR-A/B759-795[»]
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[»]
3WZDX-ray1.57A814-1172[»]
3WZEX-ray1.90A814-1172[»]
4AG8X-ray1.95A806-1171[»]
4AGCX-ray2.00A787-1171[»]
4AGDX-ray2.81A787-1171[»]
4ASDX-ray2.03A787-1171[»]
4ASEX-ray1.83A787-1171[»]
5EW3X-ray2.50A/B806-1171[»]
ProteinModelPortaliP35968.
SMRiP35968.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35968.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini46 – 110Ig-like C2-type 1Add BLAST65
Domaini141 – 207Ig-like C2-type 2Add BLAST67
Domaini224 – 320Ig-like C2-type 3Add BLAST97
Domaini328 – 414Ig-like C2-type 4Add BLAST87
Domaini421 – 548Ig-like C2-type 5Add BLAST128
Domaini551 – 660Ig-like C2-type 6Add BLAST110
Domaini667 – 753Ig-like C2-type 7Add BLAST87
Domaini834 – 1162Protein kinasePROSITE-ProRule annotationAdd BLAST329

Domaini

The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding.1 Publication

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOVERGENiHBG053432.
InParanoidiP35968.
KOiK05098.
OMAiPSYMISY.
OrthoDBiEOG091G01TL.
PhylomeDBiP35968.
TreeFamiTF325768.

Family and domain databases

Gene3Di2.60.40.10. 8 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
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]
PANTHERiPTHR24416:SF45. PTHR24416:SF45. 3 hits.
PfamiPF07679. I-set. 2 hits.
PF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR01834. VEGFRECEPTR2.
SMARTiSM00409. IG. 7 hits.
SM00408. IGc2. 5 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 7 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. 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]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P35968-1) [UniParc]FASTAAdd to basket
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.

« Hide

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

LSSPPV
Length:1,356
Mass (Da):151,527
Last modified:December 1, 2000 - v2
Checksum:i59E7C44B05CFEBB3
GO
Isoform 2 (identifier: P35968-2) [UniParc]FASTAAdd to basket
Also known as: sVegfr-2

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

Show »
Length:678
Mass (Da):75,896
Checksum:iBD4BD2686CE95EB9
GO
Isoform 3 (identifier: P35968-3) [UniParc]FASTAAdd to basket
Also known as: VEGFR2-712

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

Show »
Length:712
Mass (Da):79,634
Checksum:i1043A452AE64A528
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2Q → E in AAC16450 (Ref. 4) Curated1
Sequence conflicti772A → T in AAA59459 (PubMed:1656371).Curated1
Sequence conflicti772A → T in CAA43837 (PubMed:1656371).Curated1
Sequence conflicti787R → G in AAA59459 (PubMed:1656371).Curated1
Sequence conflicti787R → G in CAA43837 (PubMed:1656371).Curated1
Sequence conflicti835K → N in AAA59459 (PubMed:1656371).Curated1
Sequence conflicti835K → N in CAA43837 (PubMed:1656371).Curated1
Sequence conflicti1347S → T in AAA59459 (PubMed:1656371).Curated1
Sequence conflicti1347S → T in CAA43837 (PubMed:1656371).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0420532Q → R in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042054136V → M.1 PublicationCorresponds to variant rs35636987dbSNPEnsembl.1
Natural variantiVAR_042055248A → G in a renal clear cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_036126275R → L in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_022071297V → I.1 PublicationCorresponds to variant rs2305948dbSNPEnsembl.1
Natural variantiVAR_042056462L → V.1 PublicationCorresponds to variant rs56286620dbSNPEnsembl.1
Natural variantiVAR_020353472Q → H.2 PublicationsCorresponds to variant rs1870377dbSNPEnsembl.1
Natural variantiVAR_042057482C → R in HCI; associated with disease 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. 2 PublicationsCorresponds to variant rs34231037dbSNPEnsembl.1
Natural variantiVAR_042058539G → R.1 PublicationCorresponds to variant rs55716939dbSNPEnsembl.1
Natural variantiVAR_042059689T → M.1 PublicationCorresponds to variant rs34038364dbSNPEnsembl.1
Natural variantiVAR_042060814D → N.1 PublicationCorresponds to variant rs35603373dbSNPEnsembl.1
Natural variantiVAR_046679848V → E Strongly reduced autophosphorylation and kinase activity. 2 PublicationsCorresponds to variant rs1139776dbSNPEnsembl.1
Natural variantiVAR_036127873G → R in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_046680952V → I.Corresponds to variant rs13129474dbSNPEnsembl.1
Natural variantiVAR_0420611065A → T.1 PublicationCorresponds to variant rs56302315dbSNPEnsembl.1
Natural variantiVAR_0631471147P → S in HCI; somatic mutation. 1 PublicationCorresponds to variant rs121917766dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041988663 – 678ERVAP…ENQTT → GRETILDHCAEAVGMP in isoform 2. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_041989679 – 1356Missing in isoform 2. 1 PublicationAdd BLAST678
Alternative sequenceiVSP_041990712G → E in isoform 3. 1 Publication1
Alternative sequenceiVSP_041991713 – 1356Missing in isoform 3. 1 PublicationAdd BLAST644

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3497.1. [P35968-1]
PIRiJC1402.
RefSeqiNP_002244.1. NM_002253.2. [P35968-1]
UniGeneiHs.479756.

Genome annotation databases

EnsembliENST00000263923; ENSP00000263923; ENSG00000128052. [P35968-1]
GeneIDi3791.
KEGGihsa:3791.
UCSCiuc003has.4. human. [P35968-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3497.1. [P35968-1]
PIRiJC1402.
RefSeqiNP_002244.1. NM_002253.2. [P35968-1]
UniGeneiHs.479756.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1VR2X-ray2.40A806-1171[»]
1Y6AX-ray2.10A806-1171[»]
1Y6BX-ray2.10A806-1171[»]
1YWNX-ray1.71A806-1171[»]
2M59NMR-A/B759-795[»]
2METNMR-A/B/C759-795[»]
2MEUNMR-A/B759-795[»]
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[»]
3WZDX-ray1.57A814-1172[»]
3WZEX-ray1.90A814-1172[»]
4AG8X-ray1.95A806-1171[»]
4AGCX-ray2.00A787-1171[»]
4AGDX-ray2.81A787-1171[»]
4ASDX-ray2.03A787-1171[»]
4ASEX-ray1.83A787-1171[»]
5EW3X-ray2.50A/B806-1171[»]
ProteinModelPortaliP35968.
SMRiP35968.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109992. 40 interactors.
DIPiDIP-486N.
IntActiP35968. 33 interactors.
MINTiMINT-127732.
STRINGi9606.ENSP00000263923.

Chemistry databases

BindingDBiP35968.
ChEMBLiCHEMBL279.
DrugBankiDB06626. Axitinib.
DB08875. Cabozantinib.
DB09078. Lenvatinib.
DB09079. Nintedanib.
DB06589. Pazopanib.
DB08901. Ponatinib.
DB05578. Ramucirumab.
DB08896. Regorafenib.
DB00398. Sorafenib.
DB01268. Sunitinib.
GuidetoPHARMACOLOGYi1813.

PTM databases

iPTMnetiP35968.
PhosphoSitePlusiP35968.

Polymorphism and mutation databases

BioMutaiKDR.
DMDMi9087218.

Proteomic databases

EPDiP35968.
MaxQBiP35968.
PaxDbiP35968.
PeptideAtlasiP35968.
PRIDEiP35968.

Protocols and materials databases

DNASUi3791.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263923; ENSP00000263923; ENSG00000128052. [P35968-1]
GeneIDi3791.
KEGGihsa:3791.
UCSCiuc003has.4. human. [P35968-1]

Organism-specific databases

CTDi3791.
DisGeNETi3791.
GeneCardsiKDR.
HGNCiHGNC:6307. KDR.
HPAiCAB004028.
HPA030893.
MalaCardsiKDR.
MIMi191306. gene.
602089. phenotype.
neXtProtiNX_P35968.
OpenTargetsiENSG00000128052.
Orphaneti91415. Familial capillary hemangioma.
PharmGKBiPA30086.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOVERGENiHBG053432.
InParanoidiP35968.
KOiK05098.
OMAiPSYMISY.
OrthoDBiEOG091G01TL.
PhylomeDBiP35968.
TreeFamiTF325768.

Enzyme and pathway databases

BioCyciZFISH:HS05156-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-194306. Neurophilin interactions with VEGF and VEGFR.
R-HSA-195399. VEGF binds to VEGFR leading to receptor dimerization.
R-HSA-216083. Integrin cell surface interactions.
R-HSA-3928663. EPHA-mediated growth cone collapse.
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
R-HSA-5218921. VEGFR2 mediated cell proliferation.
SignaLinkiP35968.
SIGNORiP35968.

Miscellaneous databases

EvolutionaryTraceiP35968.
GeneWikiiKinase_insert_domain_receptor.
GenomeRNAii3791.
PROiP35968.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000128052.
CleanExiHS_KDR.
ExpressionAtlasiP35968. baseline and differential.
GenevisibleiP35968. HS.

Family and domain databases

Gene3Di2.60.40.10. 8 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
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]
PANTHERiPTHR24416:SF45. PTHR24416:SF45. 3 hits.
PfamiPF07679. I-set. 2 hits.
PF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR01834. VEGFRECEPTR2.
SMARTiSM00409. IG. 7 hits.
SM00408. IGc2. 5 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 7 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiVGFR2_HUMAN
AccessioniPrimary (citable) accession number: P35968
Secondary accession number(s): A2RRS0
, B5A925, C5IFA0, O60723, Q14178
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: December 1, 2000
Last modified: November 2, 2016
This is version 193 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  8. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.