DegronMD - P35968(KDR)

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. {ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:10368301, ECO:0000269|PubMed:10600473, ECO:0000269|PubMed:11387210, ECO:0000269|PubMed:12649282, ECO:0000269|PubMed:1417831, ECO:0000269|PubMed:15026417, ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:16966330, ECO:0000269|PubMed:17303569, ECO:0000269|PubMed:18529047, ECO:0000269|PubMed:19668192, ECO:0000269|PubMed:19834490, ECO:0000269|PubMed:20080685, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20705758, ECO:0000269|PubMed:21893193, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:7929439, ECO:0000269|PubMed:9160888, ECO:0000269|PubMed:9804796, ECO:0000269|PubMed:9837777}. View more >>

GO - Biological processes (BP): angiogenesis [GO:0001525]; branching involved in blood vessel morphogenesis [GO:0001569]; calcium ion homeostasis [GO:0055074]; calcium-mediated signaling using intracellular calcium source [GO:0035584]; cell fate commitment [GO:0045165]; cell maturation [GO:0048469]; cell migration [GO:0016477]; cell migration involved in sprouting angiogenesis [GO:0002042]; cellular response to hydrogen sulfide [GO:1904881]; cellular response to vascular endothelial growth factor stimulus [GO:0035924]; embryonic hemopoiesis [GO:0035162]; endocardium development [GO:0003157]; endothelial cell differentiation [GO:0045446]; endothelium development [GO:0003158]; ERK1 and ERK2 cascade [GO:0070371]; hematopoietic progenitor cell differentiation [GO:0002244]; lung alveolus development [GO:0048286]; lymph vessel development [GO:0001945]; negative regulation of apoptotic process [GO:0043066]; negative regulation of endothelial cell apoptotic process [GO:2000352]; negative regulation of gene expression [GO:0010629]; ovarian follicle development [GO:0001541]; peptidyl-tyrosine autophosphorylation [GO:0038083]; peptidyl-tyrosine phosphorylation [GO:0018108]; positive regulation of angiogenesis [GO:0045766]; positive regulation of blood vessel endothelial cell migration [GO:0043536]; positive regulation of BMP signaling pathway [GO:0030513]; positive regulation of cell migration [GO:0030335]; positive regulation of cell migration involved in sprouting angiogenesis [GO:0090050]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway [GO:0038033]; positive regulation of endothelial cell migration [GO:0010595]; positive regulation of endothelial cell proliferation [GO:0001938]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of focal adhesion assembly [GO:0051894]; positive regulation of kinase activity [GO:0033674]; positive regulation of macroautophagy [GO:0016239]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of mesenchymal cell proliferation [GO:0002053]; positive regulation of mitochondrial depolarization [GO:0051901]; positive regulation of mitochondrial fission [GO:0090141]; positive regulation of nitric-oxide synthase biosynthetic process [GO:0051770]; positive regulation of phosphatidylinositol 3-kinase signaling [GO:0014068]; positive regulation of positive chemotaxis [GO:0050927]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of vasculogenesis [GO:2001214]; post-embryonic camera-type eye morphogenesis [GO:0048597]; protein autophosphorylation [GO:0046777]; protein kinase B signaling [GO:0043491]; regulation of bone development [GO:1903010]; regulation of cell shape [GO:0008360]; regulation of hematopoietic progenitor cell differentiation [GO:1901532]; surfactant homeostasis [GO:0043129]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]; vascular endothelial growth factor receptor-2 signaling pathway [GO:0036324]; vascular endothelial growth factor receptor signaling pathway [GO:0048010]; vascular endothelial growth factor signaling pathway [GO:0038084]; vascular wound healing [GO:0061042]; vasculogenesis [GO:0001570] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.Y115D	TCGA-61-1911	OV	TCGA	DYR	CBL_MET	120:122	Mutation rewiring degron network	0.1944
p.Y115D	DO28392	OV	ICGC	DYR	CBL_MET	120:122	Mutation rewiring degron network	0.1944
p.T1339K	TCGA-64-5778	LUAD	TCGA	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.1389
p.T1339K	DO25837	LUAD	ICGC	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.1389
p.S1347L	TCGA-A5-A0G2	UCEC	TCGA	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation altering degron motif	0.7667
p.S1347L	DO41235	UCEC	ICGC	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation altering degron motif	0.7667
p.Y121C	TCGA-CA-6717	COAD	TCGA	DYR	CBL_MET	120:122	Mutation altering degron motif	0.8198
p.Y121C	DO8264	COAD	ICGC	DYR	CBL_MET	120:122	Mutation altering degron motif	0.8198
p.S1353F	TCGA-D3-A8GI	SKCM	TCGA	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.3056
p.S1353F	DO50284	SKCM	ICGC	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.3056
p.G1337S	TCGA-DF-A2KU	UCEC	TCGA	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.0833
p.G1337S	DO223286	UCEC	ICGC	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.0833
p.P1355A	TCGA-IR-A3LA	CESC	TCGA	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.25
p.P1355A	DO44377	CESC	ICGC	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.25
p.S112L	TCGA-KK-A59V	PRAD	TCGA	DYR	CBL_MET	120:122	Mutation rewiring degron network	0.1111
p.S112L	DO51346	PRAD	ICGC	DYR	CBL_MET	120:122	Mutation rewiring degron network	0.1111
p.D131A	DO8264	COAD	ICGC	DYR	CBL_MET	120:122	Mutation rewiring degron network	0.0833
p.Q119K	DO229025	LICA	ICGC	DYR	CBL_MET	120:122	Mutation rewiring degron network	0.3056
p.A127D	DO229045	LICA	ICGC	DYR	CBL_MET	120:122	Mutation rewiring degron network	0.1944
p.S1338N	DO50970	LICA	ICGC	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.1111
p.T1339I	SIDM01217	Other Blood Cancers	GDSC	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.1389
p.T1339I	SIDM00306	Non-Small Cell Lung Carcinoma	GDSC	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.1389
p.T1339I	ACH-000672	Lung Cancer	CCLE	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.1389
p.T1339I	ACH-002276	Leukemia	CCLE	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.1389
p.T1339I	ACH-002785	Unknown	CCLE	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.1389
p.T1339I	IA-LM	lung	COSMIC	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.1389
p.T1339I	MY-M12	haematopoietic and lymphoid tissue	COSMIC	DSGTTLS	DEG_SCF_TRCP1_1	1346:1352	Mutation rewiring degron network	0.1389

DegronMD: protein-targeted degradation, mutation and drug response to degrons

KDR

UniProt ID: P35968

Entrez ID: 3791

Protein name: Vascular endothelial growth factor receptor 2 (VEGFR-2) (EC 2.7.10.1) (Fetal liver kinase 1) (FLK-1) (Kinase insert domain receptor) (KDR) (Protein-tyrosine kinase receptor flk-1) (CD antigen CD309)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for KDR in