DegronMD - P17948(FLT1)

FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. Acts as a positive regulator of postnatal retinal hyaloid vessel regression (Ref.11). May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1 (PubMed:16685275). {ECO:0000269|PubMed:11141500, ECO:0000269|PubMed:11312102, ECO:0000269|PubMed:11811792, ECO:0000269|PubMed:12796773, ECO:0000269|PubMed:14633857, ECO:0000269|PubMed:15735759, ECO:0000269|PubMed:16685275, ECO:0000269|PubMed:18079407, ECO:0000269|PubMed:18515749, ECO:0000269|PubMed:18583712, ECO:0000269|PubMed:18593464, ECO:0000269|PubMed:20512933, ECO:0000269|PubMed:20551949, ECO:0000269|PubMed:21752276, ECO:0000269|PubMed:7824266, ECO:0000269|PubMed:8248162, ECO:0000269|PubMed:8605350, ECO:0000269|PubMed:9299537, ECO:0000269|Ref.11}.; FUNCTION: [Isoform 1]: Phosphorylates PLCG. {ECO:0000269|PubMed:9299537}.; FUNCTION: [Isoform 2]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 3]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 4]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 7]: Has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. {ECO:0000269|PubMed:20512933}. View more >>

GO - Biological processes (BP): 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.I1338M	TCGA-28-5207	GBM	TCGA	NSVVLYSTPP	CBL_PTK	1328:1337	Mutation rewiring degron network	0.3056
p.P1324H	TCGA-56-7730	LUSC	TCGA	PPDY	ITCH	1324:1327	Mutation altering degron motif	0.7694
p.S668C	TCGA-77-8156	LUSC	TCGA	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.1944
p.S668C	DO26802	LUSC	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.1944
p.A1319T	TCGA-A5-A0G1	UCEC	TCGA	NSVVLYSTPP	CBL_PTK	1328:1337	Mutation rewiring degron network	0.0833
p.A1319T	TCGA-A5-A0G1	UCEC	TCGA	PPDY	ITCH	1324:1327	Mutation rewiring degron network	0.1944
p.A1319T	ACH-001143	Lymphoma	CCLE	NSVVLYSTPP	CBL_PTK	1328:1337	Mutation rewiring degron network	0.0833
p.A1319T	ACH-001143	Lymphoma	CCLE	PPDY	ITCH	1324:1327	Mutation rewiring degron network	0.1944
p.D681Y	TCGA-AG-A002	READ	TCGA	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.2222
p.D1326Y	TCGA-AX-A2HC	UCEC	TCGA	PPDY	ITCH	1324:1327	Mutation altering degron motif	0.6214
p.S677A	TCGA-BR-6452	STAD	TCGA	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.7588
p.S677A	DO38404	STAD	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.7588
p.N666I	TCGA-CC-A9FU	LIHC	TCGA	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.1389
p.N666I	DO52190	LIHC	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.1389
p.T679N	TCGA-CV-7178	HNSC	TCGA	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.2778
p.T679N	DO14774	HNSC	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.2778
p.A673T	TCGA-CV-7424	HNSC	TCGA	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.7139
p.A673T	TCGA-D7-A4Z0	STAD	TCGA	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.7139
p.A673T	DO14998	HNSC	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.7139
p.A673T	DO47765	STAD	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.7139
p.I1318T	TCGA-CV-A461	HNSC	TCGA	NSVVLYSTPP	CBL_PTK	1328:1337	Mutation rewiring degron network	0.0556
p.I1318T	TCGA-CV-A461	HNSC	TCGA	PPDY	ITCH	1324:1327	Mutation rewiring degron network	0.1667
p.H670Y	TCGA-D3-A3C1	SKCM	TCGA	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.25
p.H670Y	DO47323	SKCM	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.25
p.E1315K	TCGA-EE-A29E	SKCM	TCGA	PPDY	ITCH	1324:1327	Mutation rewiring degron network	0.0833
p.K1317Q	TCGA-EE-A2GO	SKCM	TCGA	PPDY	ITCH	1324:1327	Mutation substituting flanking lysine	0.25
p.G686S	TCGA-Z2-A8RT	SKCM	TCGA	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.0833
p.G686S	DO51301	SKCM	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.0833
p.R665Q	DO229344	BTCA	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.1111
p.S675R	DO228952	LICA	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.7427
p.H683N	DO229028	LICA	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.1667
p.T678N	DO229027	LICA	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.3056
p.A684D	DO229035	LICA	ICGC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.1389
p.P705T	DO229041	LICA	ICGC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation rewiring degron network	0.1667
p.E704K	DO50882	LICA	ICGC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation rewiring degron network	0.1389
p.S714N	DO50970	LICA	ICGC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation altering degron motif	0.7069
p.G712R	DO220911	MELA	ICGC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation altering degron motif	0.6457
p.S716L	DO222363	MELA	ICGC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation rewiring degron network	0.3056
p.S716L	DO43907	UCEC	ICGC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation rewiring degron network	0.3056
p.P705H	DO46542	OV	ICGC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation rewiring degron network	0.1667
p.T711M	DO35226	PACA	ICGC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation altering degron motif	0.7423
p.T711M	DO42977	UCEC	ICGC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation altering degron motif	0.7423
p.T711M	DO41903	UCEC	ICGC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation altering degron motif	0.7423
p.P720S	DO220073	SARC	ICGC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation rewiring degron network	0.1944
p.S723A	DO41361	UCEC	ICGC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation rewiring degron network	0.1111
p.A664V	SIDM01307	Colorectal Carcinoma	GDSC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.0833
p.A673V	SIDM01016	T-Lymphoblastic Leukemia	GDSC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.5825
p.A673V	SIDM00238	Ovarian Carcinoma	GDSC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.5825
p.A673V	SIDM01263	T-Lymphoblastic Leukemia	GDSC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.5825
p.A673V	ACH-000947	Ovarian Cancer	CCLE	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.5825
p.A673V	ACH-000995	Leukemia	CCLE	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.5825
p.A673V	Jurkat	haematopoietic and lymphoid tissue	COSMIC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.5825
p.A673V	OVK-18	ovary	COSMIC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.5825
p.V721A	SIDM00193	Colorectal Carcinoma	GDSC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation rewiring degron network	0.1667
p.V721A	ACH-000991	Colon/Colorectal Cancer	CCLE	PGSST	DEG_SPOP_SBC_1	711:715	Mutation rewiring degron network	0.1667
p.V721A	SNU-81	large intestine	COSMIC	PGSST	DEG_SPOP_SBC_1	711:715	Mutation rewiring degron network	0.1667
p.T675R	SIDM01186	Breast Carcinoma	GDSC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.7876
p.T675R	UACC-893	breast	COSMIC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.7876
p.P1337A	SIDM00502	B-Lymphoblastic Leukemia	GDSC	NSVVLYSTPP	CBL_PTK	1328:1337	Mutation altering degron motif	0.7503
p.P1337A	ACH-000157	Lymphoma	CCLE	NSVVLYSTPP	CBL_PTK	1328:1337	Mutation altering degron motif	0.7503
p.P1337A	A4-Fuk	haematopoietic and lymphoid tissue	COSMIC	NSVVLYSTPP	CBL_PTK	1328:1337	Mutation altering degron motif	0.7503
p.K663N	SIDM01611	Endometrial Carcinoma	GDSC	AISSS	DEG_SPOP_SBC_1	673:677	Mutation rewiring degron network	0.0556
p.S677F	ACH-001035	Bone Cancer	CCLE	AISSS	DEG_SPOP_SBC_1	673:677	Mutation altering degron motif	0.7982
p.E723K	ACH-001408	Bladder Cancer	CCLE	PGSST	DEG_SPOP_SBC_1	711:715	Mutation rewiring degron network	0.1111
p.E719Q	ACH-002024	Colon/Colorectal Cancer	CCLE	PGSST	DEG_SPOP_SBC_1	711:715	Mutation rewiring degron network	0.2222

Kaplan plot for FLT1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

FLT1

UniProt ID: P17948

Entrez ID: 2321

Protein name: Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase FRT) (Tyrosine-protein kinase receptor FLT) (FLT) (Vascular permeability factor receptor)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for FLT1 in