Molecule Information
General Information of the Molecule (ID: Mol01832)
Name |
VEGF-2 receptor (KDR)
,Homo sapiens
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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
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Gene Name |
KDR
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Gene ID | |||||
Location |
chr4:55,078,48155,125,595 [-]
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Sequence |
MQSKVLLAVALWLCVETRAASVGLPSVSLDLPRLSIQKDILTIKANTTLQITCRGQRDLD
WLWPNNQSGSEQRVEVTECSDGLFCKTLTIPKVIGNDTGAYKCFYRETDLASVIYVYVQD YRSPFIASVSDQHGVVYITENKNKTVVIPCLGSISNLNVSLCARYPEKRFVPDGNRISWD SKKGFTIPSYMISYAGMVFCEAKINDESYQSIMYIVVVVGYRIYDVVLSPSHGIELSVGE KLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRS DQGLYTCAASSGLMTKKNSTFVRVHEKPFVAFGSGMESLVEATVGERVRIPAKYLGYPPP EIKWYKNGIPLESNHTIKAGHVLTIMEVSERDTGNYTVILTNPISKEKQSHVVSLVVYVP PQIGEKSLISPVDSYQYGTTQTLTCTVYAIPPPHHIHWYWQLEEECANEPSQAVSVTNPY PCEEWRSVEDFQGGNKIEVNKNQFALIEGKNKTVSTLVIQAANVSALYKCEAVNKVGRGE RVISFHVTRGPEITLQPDMQPTEQESVSLWCTADRSTFENLTWYKLGPQPLPIHVGELPT PVCKNLDTLWKLNATMFSNSTNDILIMELKNASLQDQGDYVCLAQDRKTKKRHCVVRQLT VLERVAPTITGNLENQTTSIGESIEVSCTASGNPPPQIMWFKDNETLVEDSGIVLKDGNR NLTIRRVRKEDEGLYTCQACSVLGCAKVEAFFIIEGAQEKTNLEIIILVGTAVIAMFFWL LLVIILRTVKRANGGELKTGYLSIVMDPDELPLDEHCERLPYDASKWEFPRDRLKLGKPL GRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVN LLGACTKPGGPLMVIVEFCKFGNLSTYLRSKRNEFVPYKTKGARFRQGKDYVGAIPVDLK RRLDSITSSQSSASSGFVEEKSLSDVEEEEAPEDLYKDFLTLEHLICYSFQVAKGMEFLA SRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDR VYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTML DCWHGEPSQRPTFSELVEHLGNLLQANAQQDGKDYIVLPISETLSMEEDSGLSLPTSPVS CMEEEEVCDPKFHYDNTAGISQYLQNSKRKSRPVSVKTFEDIPLEEPEVKVIPDDNQTDS GMVLASEELKTLEDRTKLSPSFGGMVPSKSRESVASEGSNQTSGYQSGYHSDDTDTTVYS SEEAELLKLIEIGVQTGSTAQILQPDSGTTLSSPPV Click to Show/Hide
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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 | |||||
Ensembl ID | |||||
HGNC ID | |||||
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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
Cabozantinib
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Epigenetic Alteration of DNA, RNA or Protein (EADR) | ||||
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) |
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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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Epigenetic Alteration of DNA, RNA or Protein (EADR) | ||||
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) |
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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
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Epigenetic Alteration of DNA, RNA or Protein (EADR) | ||||
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) |
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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) | ||||
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) |
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Experimental Note | Identified from the Human Clinical Data |
Preclinical Drug(s)
1 drug(s) in total
Unspecified VEGFR2 antibody
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Regulation by the Disease Microenvironment (RTDM) | ||||
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) |
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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
Melanoma [ICD-11: 2C30]
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
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Disease-specific Molecule Abundances | Click to View the Clearer Original Diagram | |
Tissue-specific Molecule Abundances in Healthy Individuals
References
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