HCSGD entry for KDR
1. General information
| Official gene symbol | KDR |
|---|---|
| Entrez ID | 3791 |
| Gene full name | kinase insert domain receptor (a type III receptor tyrosine kinase) |
| Other gene symbols | CD309 FLK1 VEGFR VEGFR2 |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
This gene isn't in PPI subnetwork.
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0001525 | Angiogenesis | TAS | biological_process |
| GO:0001541 | Ovarian follicle development | IEA | biological_process |
| GO:0001570 | Vasculogenesis | ISS | biological_process |
| GO:0001934 | Positive regulation of protein phosphorylation | IDA | biological_process |
| GO:0001938 | Positive regulation of endothelial cell proliferation | IMP | biological_process |
| GO:0001945 | Lymph vessel development | IEA | biological_process |
| GO:0002042 | Cell migration involved in sprouting angiogenesis | ISS | biological_process |
| GO:0002053 | Positive regulation of mesenchymal cell proliferation | IEA | biological_process |
| GO:0003158 | Endothelium development | ISS | biological_process |
| GO:0004713 | Protein tyrosine kinase activity | IDA | molecular_function |
| GO:0004714 | Transmembrane receptor protein tyrosine kinase activity | TAS | molecular_function |
| GO:0004716 | Receptor signaling protein tyrosine kinase activity | TAS | molecular_function |
| GO:0005021 | Vascular endothelial growth factor-activated receptor activity | IDA | molecular_function |
| GO:0005178 | Integrin binding | IPI | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005524 | ATP binding | IEA | molecular_function |
| GO:0005576 | Extracellular region | IEA | cellular_component |
| GO:0005634 | Nucleus | IEA | cellular_component |
| GO:0005768 | Endosome | IDA | cellular_component |
| GO:0005769 | Early endosome | ISS | cellular_component |
| GO:0005794 | Golgi apparatus | IDA | cellular_component |
| GO:0005886 | Plasma membrane | IDA ISS TAS | cellular_component |
| GO:0005887 | Integral component of plasma membrane | IDA | cellular_component |
| GO:0007169 | Transmembrane receptor protein tyrosine kinase signaling pathway | TAS | biological_process |
| GO:0008284 | Positive regulation of cell proliferation | IDA IMP | biological_process |
| GO:0008360 | Regulation of cell shape | IDA | biological_process |
| GO:0009897 | External side of plasma membrane | IEA | cellular_component |
| GO:0010595 | Positive regulation of endothelial cell migration | IMP | biological_process |
| GO:0014068 | Positive regulation of phosphatidylinositol 3-kinase signaling | IDA | biological_process |
| GO:0016023 | Cytoplasmic membrane-bounded vesicle | IEA | cellular_component |
| GO:0016032 | Viral process | IEA | biological_process |
| GO:0018108 | Peptidyl-tyrosine phosphorylation | IDA | biological_process |
| GO:0019838 | Growth factor binding | IPI | molecular_function |
| GO:0023014 | Signal transduction by phosphorylation | TAS | biological_process |
| GO:0030054 | Cell junction | ISS | cellular_component |
| GO:0030335 | Positive regulation of cell migration | IDA IMP | biological_process |
| GO:0035162 | Embryonic hemopoiesis | ISS | biological_process |
| GO:0035584 | Calcium-mediated signaling using intracellular calcium source | IMP | biological_process |
| GO:0035924 | Cellular response to vascular endothelial growth factor stimulus | IDA IMP | biological_process |
| GO:0038083 | Peptidyl-tyrosine autophosphorylation | ISS | biological_process |
| GO:0038084 | Vascular endothelial growth factor signaling pathway | IDA | biological_process |
| GO:0038085 | Vascular endothelial growth factor binding | IPI | molecular_function |
| GO:0043066 | Negative regulation of apoptotic process | IMP | biological_process |
| GO:0043129 | Surfactant homeostasis | IEA | biological_process |
| GO:0043410 | Positive regulation of MAPK cascade | IDA | biological_process |
| GO:0045121 | Membrane raft | IDA | cellular_component |
| GO:0045165 | Cell fate commitment | IEA | biological_process |
| GO:0045446 | Endothelial cell differentiation | IEA | biological_process |
| GO:0045766 | Positive regulation of angiogenesis | IMP | biological_process |
| GO:0046777 | Protein autophosphorylation | IDA | biological_process |
| GO:0048010 | Vascular endothelial growth factor receptor signaling pathway | IDA TAS | biological_process |
| GO:0048286 | Lung alveolus development | IEA | biological_process |
| GO:0048469 | Cell maturation | IEA | biological_process |
| GO:0048754 | Branching morphogenesis of an epithelial tube | IEA | biological_process |
| GO:0050927 | Positive regulation of positive chemotaxis | IDA | biological_process |
| GO:0051770 | Positive regulation of nitric-oxide synthase biosynthetic process | IDA IMP | biological_process |
| GO:0051879 | Hsp90 protein binding | TAS | molecular_function |
| GO:0051894 | Positive regulation of focal adhesion assembly | IDA | biological_process |
| GO:0055074 | Calcium ion homeostasis | IEA | biological_process |
| GO:0070374 | Positive regulation of ERK1 and ERK2 cascade | IMP | biological_process |
| GO:2000352 | Negative regulation of endothelial cell apoptotic process | IDA | biological_process |
| GO:2001214 | Positive regulation of vasculogenesis | ISS | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.3631949014 | 0.8404457581 | 0.9999902473 | 1.0000000000 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Up | 0.5467298637 |
| GSE13712_SHEAR | Up | 0.0299139443 |
| GSE13712_STATIC | Down | -0.0798651746 |
| GSE19018 | Up | 0.1779766242 |
| GSE19899_A1 | Up | 0.1134487867 |
| GSE19899_A2 | Up | 0.0290171418 |
| PubMed_21979375_A1 | Down | -0.0851291150 |
| PubMed_21979375_A2 | Up | 0.2465535848 |
| GSE35957 | Up | 0.1741875864 |
| GSE36640 | Up | 0.0825930859 |
| GSE54402 | Down | -0.1098840427 |
| GSE9593 | Down | -0.0757230961 |
| GSE43922 | Up | 0.0464771681 |
| GSE24585 | Up | 0.3208241192 |
| GSE37065 | Down | -0.1632788493 |
| GSE28863_A1 | Down | -0.0824691324 |
| GSE28863_A2 | Up | 0.0011597889 |
| GSE28863_A3 | Up | 0.1469773995 |
| GSE28863_A4 | Down | -0.0624699212 |
| GSE48662 | Down | -0.0963231605 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
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- Drugs
Name | Drug | Accession number |
|---|---|---|
| Sorafenib | DB00398 | APRD01304 | DB07438 |
| Sunitinib | DB01268 | DB07417 |
| N-(4-{4-AMINO-6-[4-(METHYLOXY)PHENYL]FURO[2,3-D]PYRIMIDIN-5-YL}PHENYL)-N'-[2-FLUORO-5-(TRIFLUOROMETHYL)PHENYL]UREA | DB04727 | - |
| AZD2171 | DB04849 | - |
| Vatalanib | DB04879 | - |
| XL999 | DB05014 | - |
| XL880 | DB05030 | - |
| TG100801 | DB05075 | - |
| XL820 | DB05146 | - |
| XL184 | DB05153 | - |
| CYC116 | DB05198 | - |
| Ramucirumab | DB05578 | - |
| ABT-869 | DB06080 | - |
| IMC-1C11 | DB06101 | - |
| Pazopanib | DB06589 | - |
| Axitinib | DB06626 | - |
| 4-[[2-[[4-chloro-3-(trifluoromethyl)phenyl]amino]-3H-benzimidazol-5-yl]oxy]-N-methyl-pyridine-2-carboxamide | DB06938 | - |
| N-(4-phenoxyphenyl)-2-[(pyridin-4-ylmethyl)amino]nicotinamide | DB07183 | - |
| N-cyclopropyl-6-[(6,7-dimethoxyquinolin-4-yl)oxy]naphthalene-1-carboxamide | DB07274 | - |
| 6-chloro-N-pyrimidin-5-yl-3-{[3-(trifluoromethyl)phenyl]amino}-1,2-benzisoxazole-7-carboxamide | DB07326 | - |
| N-(CYCLOPROPYLMETHYL)-4-(METHYLOXY)-3-({5-[3-(3-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-YL}AMINO)BENZENESULFONAMIDE | DB07333 | - |
| N-[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-AMINE | DB07334 | - |
| 3-(2-aminoquinazolin-6-yl)-1-(3,3-dimethylindolin-6-yl)-4-methylpyridin-2(1H)-one | DB07514 | - |
| 3-(2-aminoquinazolin-6-yl)-4-methyl-1-[3-(trifluoromethyl)phenyl]pyridin-2(1H)-one | DB07528 | - |
| N'-(6-aminopyridin-3-yl)-N-(2-cyclopentylethyl)-4-methyl-benzene-1,3-dicarboxamide | DB07537 | - |
| N~4~-methyl-N~4~-(3-methyl-1H-indazol-6-yl)-N~2~-(3,4,5-trimethoxyphenyl)pyrimidine-2,4-diamine | DB08042 | - |
| N~4~-(3-methyl-1H-indazol-6-yl)-N~2~-(3,4,5-trimethoxyphenyl)pyrimidine-2,4-diamine | DB08519 | - |
| Cabozantinib | DB08875 | - |
| Regorafenib | DB08896 | - |
| Ponatinib | DB08901 | - |
| Lenvatinib | DB09078 | - |
| Nintedanib | DB09079 | - |
- MicroRNAs
- mirTarBase
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-200b-3p | MIMAT0000318 | MIRT006442 | Luciferase reporter assay//Western blot | Functional MTI | 21544626 |
| hsa-miR-19b-1-5p | MIMAT0004491 | MIRT006277 | Luciferase reporter assay | Non-Functional MTI | 22197821 |
| hsa-miR-335-5p | MIMAT0000765 | MIRT016978 | Microarray | Functional MTI (Weak) | 18185580 |
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- mirRecord
- mirRecord
MicroRNA name | mirBase ID | Target site number | MiRNA mature ID | Test method inter | MiRNA regulation site | Reporter target site | Pubmed ID |
|---|---|---|---|---|---|---|---|
| hsa-miR-16-5p | MIMAT0000069 | 1 | hsa-miR-16 | {Western blot} | {overexpression by miRNA mimics tranfection} | 21885851 | |
| hsa-miR-424-5p | MIMAT0001341 | NA | hsa-miR-424 | {Western blot} | {overexpression by miRNA mimics tranfection} | 21885851 |
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6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 16 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 26420897 | METHODS: Mining of The Cancer Genome Atlas prompted us to test whether GBM cells in culture, which express EGFRvIII, selectively express vascular endothelial growth factor receptor (VEGFR)2 |
| 26420897 | We then applied multiple approaches to test the effects of VEGFR2 on GBM cell growth, apoptosis, and cellular senescence |
| 26420897 | RESULTS: In human GBM, EGFR overexpression and EGFRvIII positivity were associated with increased VEGFR2 expression |
| 26420897 | In GBM cells in culture, EGFRvIII-initiated cell signaling increased expression of VEGFR2, which prevented cellular senescence and promoted cell cycle progression |
| 26420897 | Similar results were obtained when VEGFR2 was silenced |
| 26420897 | CONCLUSIONS: VEGFR2 expression by GBM cells supports cell cycle progression and prevents cellular senescence |
| 26420897 | Coexpression of VEGFR2 by GBM cells in which EGFR signaling is activated may contribute to the aggressive nature of these cells |
| 25874702 | At day-2 and day-7 after AMI onset, circulating-EPCs (CD34+ Flk1+) were quantified by flow cytometry |
| 25797700 | VEGFR2 Signaling Prevents Colorectal Cancer Cell Senescence to Promote Tumorigenesis in Mice With Colitis |
| 25797700 | We investigated whether vascular endothelial growth factor (VEGF) signaling via its receptor, VEGFR2, regulates senescence and proliferation of tumor cells in mice with colitis-associated cancer (CAC) |
| 25797700 | METHODS: CAC was induced in VEGFR2(DeltaIEC) mice, which do not express VEGFR2 in the intestinal epithelium, and VEGFR2(fl/fl) mice (controls) by administration of azoxymethane followed by dextran sodium sulfate |
| 25797700 | We found VEGFR2 to activate phosphatidylinositol-4,5-bisphosphate-3-kinase and AKT, resulting in inactivation of p21 in HCT116 cells |
| 25797700 | Inhibitors of VEGFR2 and AKT induced senescence in HCT116 cells |
| 25797700 | CONCLUSIONS: Inhibition of VEGFR2 signaling leads to senescence of human and mouse colorectal cancer cells |
| 25797700 | VEGFR2 interacts with phosphatidylinositol-4,5-bisphosphate-3-kinase and AKT to inactivate p21 |
| 25693733 | Fucoidan-preconditioning of senescent ECFCs was shown by flow cytometry to restore the expression of functional ECFC surface markers (CD34, c-Kit, VEGFR2, and CXCR4) and stimulate the in vitro tube formation capacity of ECFCs |
| 25407160 | In the mouse hind limb ischemia model, TUDCA promoted blood perfusion by enhancing angiogenesis through recruitment of Flk-1(+) /CD34(+) and Sca-1(+) /c-kit(+) progenitors into damaged tissue |
| 25192254 | The expression of VEGF and VEGFR2 was reduced in Sirt3KO-EPCs |
| 24804814 | OBJECTIVE: As the new oral selective VEGFR tyrosine kinase inhibitor, axitinib (AG-013736) exerts powerful antitumor activity in multiple solid tumors, while its' effect was unclear in gastric cancer |
| 21730299 | Cellular senescence impaired angiogenic functions in ECs without attenuating the mitogen-activated protein kinase or Akt signaling, and vascular endothelial growth factor receptor 2 or Tie-2 expressions |
| 21618508 | Similar results were also obtained from cells treated with a VEGFR2 kinase inhibitor Ki8751 |
| 21245959 | This study investigated the effects of short- and long-term in vitro inhibition of vascular endothelial growth factor (VEGF) Receptor-2 (VEGFR-2) signaling by SU5416 and other inhibitors of the VEGF signaling pathway in OECs |
| 21245959 | Naturally senescent cells and cells rendered senescent by VEGFR-2 TKIs had reduced VEGFR-2 and CXCR-4 expression and demonstrated reduced migratory ability to VEGF |
| 20424141 | Results of flow cytometry showed that EPCs after 7 days of culture expressed both stem cell markers CD34 and CD133 and endothelial cell markers VEGFR-2 (flk-1) and VE-cadherin |
| 19723023 | Vascular reactive hyperaemic FBF response, resting CD34+ and CD34+/VEGFR2+ (vascular endothelial growth factor receptor 2+] cell number, CFU-EC (colony forming unit-endothelial cell) count and CFU-EC senescence were evaluated |
| 18583712 | Vascular endothelial growth factor (VEGF) binds both VEGF receptor-1 (VEGFR-1) and VEGF receptor-2 (VEGFR-2) |
| 18583712 | Activation of VEGFR-2 is thought to play a major role in the regulation of endothelial function by VEGF |
| 18583712 | We examined the effects of retroviral vectors expressing a small interference RNA that targeted either the VEGFR-1 gene or the VEGFR-2 gene |
| 18583712 | Deletion of either VEGFR-1 or VEGFR-2 reduced the ability of endothelial cells to form capillaries |
| 18583712 | In contrast, deletion of VEGFR-2 significantly impaired endothelial cell survival |
| 18355322 | Even when cultured for two months, the cells maintained endothelial cell properties, as assessed by expression of endothelium-specific markers and intracellular signaling through the vascular endothelial growth factor receptors VEGFR-2 and VEGFR-3, as well as their physiological characteristics |
| 17606438 | Senescence-unrelated impediment of osteogenesis from Flk1+ bone marrow mesenchymal stem cells induced by total body irradiation and its contribution to long-term bone and hematopoietic injury |
| 17606438 | DESIGN AND METHODS: At different time points after TBI, Flk1+ MSC were isolated from BM of male C57BL/6 mice and analyzed for colony forming units-fibroblast (CFU-F), cellular senescence-related indices and osteogenic potential |
| 16154800 | In the area of new drug development, a recurrent theme was receptor tyrosine kinase (TK) inhibitors, with multi-targeted, small molecule inhibitors - highly potent against a family of receptors such as vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor (PDGFR) and the receptor tyrosine kinase KIT - taking centre stage |
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