General Information of the Molecule (ID: Mol01832)
Name
VEGF-2 receptor (KDR) ,Homo sapiens
Synonyms
VEGFR-2; Fetal liver kinase 1; FLK-1; Kinase insert domain receptor; KDR; Protein-tyrosine kinase receptor flk-1; CD antigen CD309; KDR; FLK1; VEGFR2
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Molecule Type
Protein
Gene Name
KDR
Gene ID
3791
Location
chr4:55,078,48155,125,595 [-]
Sequence
MQSKVLLAVALWLCVETRAASVGLPSVSLDLPRLSIQKDILTIKANTTLQITCRGQRDLD
WLWPNNQSGSEQRVEVTECSDGLFCKTLTIPKVIGNDTGAYKCFYRETDLASVIYVYVQD
YRSPFIASVSDQHGVVYITENKNKTVVIPCLGSISNLNVSLCARYPEKRFVPDGNRISWD
SKKGFTIPSYMISYAGMVFCEAKINDESYQSIMYIVVVVGYRIYDVVLSPSHGIELSVGE
KLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRS
DQGLYTCAASSGLMTKKNSTFVRVHEKPFVAFGSGMESLVEATVGERVRIPAKYLGYPPP
EIKWYKNGIPLESNHTIKAGHVLTIMEVSERDTGNYTVILTNPISKEKQSHVVSLVVYVP
PQIGEKSLISPVDSYQYGTTQTLTCTVYAIPPPHHIHWYWQLEEECANEPSQAVSVTNPY
PCEEWRSVEDFQGGNKIEVNKNQFALIEGKNKTVSTLVIQAANVSALYKCEAVNKVGRGE
RVISFHVTRGPEITLQPDMQPTEQESVSLWCTADRSTFENLTWYKLGPQPLPIHVGELPT
PVCKNLDTLWKLNATMFSNSTNDILIMELKNASLQDQGDYVCLAQDRKTKKRHCVVRQLT
VLERVAPTITGNLENQTTSIGESIEVSCTASGNPPPQIMWFKDNETLVEDSGIVLKDGNR
NLTIRRVRKEDEGLYTCQACSVLGCAKVEAFFIIEGAQEKTNLEIIILVGTAVIAMFFWL
LLVIILRTVKRANGGELKTGYLSIVMDPDELPLDEHCERLPYDASKWEFPRDRLKLGKPL
GRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVN
LLGACTKPGGPLMVIVEFCKFGNLSTYLRSKRNEFVPYKTKGARFRQGKDYVGAIPVDLK
RRLDSITSSQSSASSGFVEEKSLSDVEEEEAPEDLYKDFLTLEHLICYSFQVAKGMEFLA
SRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDR
VYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTML
DCWHGEPSQRPTFSELVEHLGNLLQANAQQDGKDYIVLPISETLSMEEDSGLSLPTSPVS
CMEEEEVCDPKFHYDNTAGISQYLQNSKRKSRPVSVKTFEDIPLEEPEVKVIPDDNQTDS
GMVLASEELKTLEDRTKLSPSFGGMVPSKSRESVASEGSNQTSGYQSGYHSDDTDTTVYS
SEEAELLKLIEIGVQTGSTAQILQPDSGTTLSSPPV
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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.
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Uniprot ID
VGFR2_HUMAN
Ensembl ID
ENSG00000128052
HGNC ID
HGNC:6307
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule
  ADTT: Aberration of the Drug's Therapeutic Target
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  RTDM: Regulation by the Disease Microenvironment
Drug Resistance Data Categorized by Drug
Approved Drug(s)
3 drug(s) in total
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Cabozantinib
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: Colorectal cancer [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cabozantinib
Molecule Alteration Missense mutation
p.R1032Q (c.3095G>A)
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation VEGF signaling pathway Activation hsa04370
In Vitro Model Colo-320 cells Colon Homo sapiens (Human) CVCL_1989
MDST8 cells Colon Homo sapiens (Human) CVCL_2588
In Vivo Model Nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration
BEAMing assay; Western blotting analysis; immunofluorescence assay
Experiment for
Drug Resistance
Promega assay
Mechanism Description VEGFR2 is somatically mutated across tumor types and that VEGFR2 mutants can be oncogenic and control sensitivity/resistance to antiangiogenic drugs.
Lenvatinib
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: Colorectal cancer [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Lenvatinib
Molecule Alteration Missense mutation
p.R1032Q (c.3095G>A)
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation VEGF signaling pathway Activation hsa04370
In Vitro Model Colo-320 cells Colon Homo sapiens (Human) CVCL_1989
MDST8 cells Colon Homo sapiens (Human) CVCL_2588
In Vivo Model Nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration
BEAMing assay; Western blotting analysis; immunofluorescence assay
Experiment for
Drug Resistance
Promega assay
Mechanism Description VEGFR2 is somatically mutated across tumor types and that VEGFR2 mutants can be oncogenic and control sensitivity/resistance to antiangiogenic drugs.
Regorafenib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: Colorectal cancer [1]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Regorafenib
Molecule Alteration Missense mutation
p.L840F (c.2518C>T)
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation VEGF signaling pathway Inhibition hsa04370
In Vitro Model Colo-320 cells Colon Homo sapiens (Human) CVCL_1989
MDST8 cells Colon Homo sapiens (Human) CVCL_2588
In Vivo Model Nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration
BEAMing assay; Western blotting analysis; immunofluorescence assay
Experiment for
Drug Resistance
Promega assay
Mechanism Description VEGFR2 is somatically mutated across tumor types and that VEGFR2 mutants can be oncogenic and control sensitivity/resistance to antiangiogenic drugs.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Colorectal cancer [2]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Regorafenib
Molecule Alteration Missense mutation
p.R961W (c.2881C>T)
Experimental Note Identified from the Human Clinical Data
Preclinical Drug(s)
1 drug(s) in total
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Unspecified VEGFR2 antibody
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Disease Class: Melanoma [3]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
Sensitive Drug Unspecified VEGFR2 antibody
Molecule Alteration Missense mutation
p.Q472H (c.1416A>T)
Experimental Note Identified from the Human Clinical Data
In Vitro Model WM3248 cells Skin Homo sapiens (Human) CVCL_6798
WM1575 cells Skin Homo sapiens (Human) CVCL_L027
Experiment for
Molecule Alteration
Targeted NGS assay
Experiment for
Drug Resistance
Proliferation assay; Invasion assay
Disease- and Tissue-specific Abundances of This Molecule
ICD Disease Classification 02
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Melanoma [ICD-11: 2C30]
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Differential expression of molecule in resistant diseases
The Studied Tissue Skin
The Specified Disease Melanoma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 1.84E-01; Fold-change: 1.99E-01; Z-score: 1.49E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Tissue-specific Molecule Abundances in Healthy Individuals
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References
Ref 1 Exome Sequencing of Plasma DNA Portrays the Mutation Landscape of Colorectal Cancer and Discovers Mutated VEGFR2 Receptors as Modulators of Antiangiogenic TherapiesClin Cancer Res. 2018 Aug 1;24(15):3550-3559. doi: 10.1158/1078-0432.CCR-18-0103. Epub 2018 Mar 27.
Ref 2 KDR Mutation as a Novel Predictive Biomarker of Exceptional Response to Regorafenib in Metastatic Colorectal CancerCureus. 2016 Feb 3;8(2):e478. doi: 10.7759/cureus.478.
Ref 3 Identification of a Novel Pathogenic Germline KDR Variant in MelanomaClin Cancer Res. 2016 May 15;22(10):2377-85. doi: 10.1158/1078-0432.CCR-15-1811. Epub 2015 Dec 2.

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