ID:VGFR1_HUMAN DESCRIPTION: RecName: Full=Vascular endothelial growth factor receptor 1; Short=VEGFR-1; EC=2.7.10.1; AltName: Full=Fms-like tyrosine kinase 1; Short=FLT-1; AltName: Full=Tyrosine-protein kinase FRT; AltName: Full=Tyrosine-protein kinase receptor FLT; Short=FLT; AltName: Full=Vascular permeability factor receptor; Flags: Precursor; 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. 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. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. 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. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFB or PGF leads to dimerization and activation by autophosphorylation on tyrosine residues. SUBUNIT: Interacts with VEGFA, VEGFB and PGF. Monomer in the absence of bound VEGFA, VEGFB or PGF. Homodimer in the presence of bound VEGFA, VEGFB and PGF. Can also form a heterodimer with KDR. Interacts (when tyrosine phosphorylated) with CBL, CRK, GRB2, NCK1, PIK3R1, PLCG, PSEN1 and PTPN11. Probably interacts also with PTPRB. Interacts with GNB2L1/RACK1. Identified in a complex with CBL and CD2AP. INTERACTION: P15692:VEGFA; NbExp=2; IntAct=EBI-1026718, EBI-1026643; SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I membrane protein. Endosome. Note=Autophosphorylation promotes ubiquitination and endocytosis. SUBCELLULAR LOCATION: Isoform 2: Secreted. SUBCELLULAR LOCATION: Isoform 3: Secreted. SUBCELLULAR LOCATION: Isoform 4: Secreted. SUBCELLULAR LOCATION: Isoform 5: Cytoplasm (Potential). SUBCELLULAR LOCATION: Isoform 6: Cytoplasm (Potential). SUBCELLULAR LOCATION: Isoform 7: Cytoplasm (Potential). TISSUE SPECIFICITY: Detected in normal lung, but also in placenta, liver, kidney, heart and brain tissues. Specifically expressed in most of the vascular endothelial cells, and also expressed in peripheral blood monocytes. Isoform 2 is strongly expressed in placenta. Isoform 3 is expressed in corneal epithelial cells (at protein level). Isoform 3 is expressed in vascular smooth muscle cells (VSMC). INDUCTION: Up-regulated in coculture of VSMC/endothelial cell (EC) or by direct exposure to VEGF of VSMC monoculture. Up-regulated from the second trimester of pregnancy to the term and in the placenta of women with preeclampsia (PE). Up-regulated in monocytes exposed to bacterial lipopolysaccharide (LPS). DOMAIN: The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFA binding. PTM: N-glycosylated. PTM: Ubiquitinated after VEGFA-mediated autophosphorylation, leading to proteolytic degradation. PTM: Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-1169 is important for interaction with PLCG. Phosphorylation at Tyr-1213 is important for interaction with PIK3R1, PTPN11, GRB2, and PLCG. Phosphorylation at Tyr-1333 is important for endocytosis and for interaction with CBL, NCK1 and CRK. Is probably dephosphorylated by PTPRB. DISEASE: Note=Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages. DISEASE: Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. SIMILARITY: Contains 7 Ig-like C2-type (immunoglobulin-like) domains. SIMILARITY: Contains 1 protein kinase domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P17948
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
LQ882906 - Sequence 55 from Patent WO2018160841. X51602 - Human flt mRNA for receptor-related tyrosine kinase. AF063657 - Homo sapiens vascular endothelial growth factor receptor (FLT1) mRNA, complete cds. AB385191 - Synthetic construct DNA, clone: pF1KB9075, Homo sapiens FLT1 gene for vascular endothelial growth factor receptor 1 precursor, complete cds, without stop codon, in Flexi system. EU360600 - Homo sapiens psVEGFR1p mRNA, complete cds. EU368830 - Homo sapiens soluble VEGF receptor 1-14 (FLT1) mRNA, complete cds. LQ487916 - Sequence 25 from Patent WO2016083623. AK300392 - Homo sapiens cDNA FLJ60350 complete cds, highly similar to Vascular endothelial growth factor receptor 1precursor (EC 2.7.10.1). AK309901 - Homo sapiens cDNA, FLJ99942. U01134 - Human soluble vascular endothelial cell growth factor receptor (sflt) mRNA, complete cds. AK292936 - Homo sapiens cDNA FLJ76691 complete cds, highly similar to Homo sapiens fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor), mRNA. BC039007 - Homo sapiens fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor), mRNA (cDNA clone MGC:47768 IMAGE:5722772), complete cds. KJ891186 - Synthetic construct Homo sapiens clone ccsbBroadEn_00580 FLT1 gene, encodes complete protein. KR712039 - Synthetic construct Homo sapiens clone CCSBHm_00034991 FLT1 (FLT1) mRNA, encodes complete protein. S77812 - flt=vascular endothelial growth factor receptor/VEGF receptor/cell surface tyrosine kinase {clone FLT14} [human, ovarian carcinoma ascitic cells, mRNA Partial Mutant, 338 nt]. S77814 - flt=vascular endothelial growth factor receptor/VEGF receptor/cell surface tyrosine kinase {clone FLT15} [human, ovarian carcinoma ascitic cells, mRNA Partial Mutant, 358 nt]. MP584556 - Sequence 55 from Patent WO2020081767. JD087294 - Sequence 68318 from Patent EP1572962. JD038925 - Sequence 19949 from Patent EP1572962. JD284177 - Sequence 265201 from Patent EP1572962. JD119806 - Sequence 100830 from Patent EP1572962. JD041081 - Sequence 22105 from Patent EP1572962. JD051646 - Sequence 32670 from Patent EP1572962. JD040303 - Sequence 21327 from Patent EP1572962. JD168836 - Sequence 149860 from Patent EP1572962. JD528335 - Sequence 509359 from Patent EP1572962. JD320161 - Sequence 301185 from Patent EP1572962. JD329281 - Sequence 310305 from Patent EP1572962. JD314625 - Sequence 295649 from Patent EP1572962. JD508274 - Sequence 489298 from Patent EP1572962. JD043550 - Sequence 24574 from Patent EP1572962. JD101268 - Sequence 82292 from Patent EP1572962. JD173992 - Sequence 155016 from Patent EP1572962. JD241255 - Sequence 222279 from Patent EP1572962. JD203349 - Sequence 184373 from Patent EP1572962. JD278725 - Sequence 259749 from Patent EP1572962. JD262234 - Sequence 243258 from Patent EP1572962. JD359330 - Sequence 340354 from Patent EP1572962. JD048651 - Sequence 29675 from Patent EP1572962. JD404138 - Sequence 385162 from Patent EP1572962. JD215063 - Sequence 196087 from Patent EP1572962. JD363557 - Sequence 344581 from Patent EP1572962. JD040679 - Sequence 21703 from Patent EP1572962. JD524076 - Sequence 505100 from Patent EP1572962. JD345094 - Sequence 326118 from Patent EP1572962. JD565591 - Sequence 546615 from Patent EP1572962. JD347088 - Sequence 328112 from Patent EP1572962. JD270240 - Sequence 251264 from Patent EP1572962. JD217971 - Sequence 198995 from Patent EP1572962. JD134077 - Sequence 115101 from Patent EP1572962. JD060678 - Sequence 41702 from Patent EP1572962. JD439260 - Sequence 420284 from Patent EP1572962. JD515352 - Sequence 496376 from Patent EP1572962. AB209050 - Homo sapiens mRNA for fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor) variant protein. JD382724 - Sequence 363748 from Patent EP1572962. JD433343 - Sequence 414367 from Patent EP1572962. JF509745 - Homo sapiens p28FLT1 (FLT1) mRNA, complete cds, alternatively spliced. JF509744 - Homo sapiens p19FLT1 (FLT1) mRNA, complete cds, alternatively spliced. EF491869 - Homo sapiens intracellular domain VEGFR1 variant 21 mRNA, complete cds, alternatively spliced. EF491870 - Homo sapiens intracellular domain VEGFR1 variant 21 mRNA, complete cds, alternatively spliced. EF491868 - Homo sapiens intrecellular domain VEGFR1 variant 18 mRNA, complete cds. DQ836394 - Homo sapiens idVEGFR-1 (FLT1) mRNA, complete cds. DQ836395 - Homo sapiens N2idVEGFR-1 (FLT1) mRNA, complete cds. DQ836396 - Homo sapiens tVEGFR-1 (FLT1) mRNA, partial cds. EU443152 - Homo sapiens soluble FLT1 variant e15a (FLT1) mRNA, partial cds, alternatively spliced. AF339822 - Homo sapiens clone IMAGE:451939, mRNA sequence. LQ650717 - Sequence 64 from Patent WO2016161378. LQ650836 - Sequence 183 from Patent WO2016161378. LQ654986 - Sequence 81 from Patent WO2016161388. MA410039 - JP 2018517429-A/81: FULLY STABILIZED ASYMMETRIC SIRNA. EU826561 - Homo sapiens soluble VEGFR1 variant 21 (VEGFR1) mRNA, complete cds, alternatively spliced. LQ650894 - Sequence 241 from Patent WO2016161378. LQ655044 - Sequence 139 from Patent WO2016161388. LQ650835 - Sequence 182 from Patent WO2016161378. LQ654985 - Sequence 80 from Patent WO2016161388. LQ650893 - Sequence 240 from Patent WO2016161378. LQ655043 - Sequence 138 from Patent WO2016161388. LQ650892 - Sequence 239 from Patent WO2016161378. LQ655042 - Sequence 137 from Patent WO2016161388. LQ650891 - Sequence 238 from Patent WO2016161378. LQ655041 - Sequence 136 from Patent WO2016161388. LQ650834 - Sequence 181 from Patent WO2016161378. LQ654984 - Sequence 79 from Patent WO2016161388. LQ650833 - Sequence 180 from Patent WO2016161378. LQ654983 - Sequence 78 from Patent WO2016161388. LQ650832 - Sequence 179 from Patent WO2016161378. LQ654982 - Sequence 77 from Patent WO2016161388. LQ650889 - Sequence 236 from Patent WO2016161378. LQ655039 - Sequence 134 from Patent WO2016161388. LQ650888 - Sequence 235 from Patent WO2016161378. LQ655038 - Sequence 133 from Patent WO2016161388. LQ650830 - Sequence 177 from Patent WO2016161378. LQ654980 - Sequence 75 from Patent WO2016161388. LQ650829 - Sequence 176 from Patent WO2016161378. LQ654979 - Sequence 74 from Patent WO2016161388. EU826562 - Homo sapiens soluble VEGFR1 variant 2 (VEGFR1) mRNA, complete cds, alternatively spliced. BC029849 - Homo sapiens fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor), mRNA (cDNA clone IMAGE:5176591), with apparent retained intron. LQ650887 - Sequence 234 from Patent WO2016161378. LQ655037 - Sequence 132 from Patent WO2016161388. LQ650828 - Sequence 175 from Patent WO2016161378. LQ654978 - Sequence 73 from Patent WO2016161388. LQ650886 - Sequence 233 from Patent WO2016161378. LQ655036 - Sequence 131 from Patent WO2016161388. LQ650885 - Sequence 232 from Patent WO2016161378. LQ655035 - Sequence 130 from Patent WO2016161388. LQ650827 - Sequence 174 from Patent WO2016161378. LQ654977 - Sequence 72 from Patent WO2016161388. LQ650884 - Sequence 231 from Patent WO2016161378. LQ655034 - Sequence 129 from Patent WO2016161388. BC046165 - Homo sapiens, clone IMAGE:5192014, mRNA, partial cds. BC048278 - Homo sapiens, clone IMAGE:5192302, mRNA, partial cds. LQ650824 - Sequence 171 from Patent WO2016161378. LQ654974 - Sequence 69 from Patent WO2016161388. JD444011 - Sequence 425035 from Patent EP1572962. MA410097 - JP 2018517429-A/139: FULLY STABILIZED ASYMMETRIC SIRNA. MA410038 - JP 2018517429-A/80: FULLY STABILIZED ASYMMETRIC SIRNA. MA410096 - JP 2018517429-A/138: FULLY STABILIZED ASYMMETRIC SIRNA. MA410095 - JP 2018517429-A/137: FULLY STABILIZED ASYMMETRIC SIRNA. MA410094 - JP 2018517429-A/136: FULLY STABILIZED ASYMMETRIC SIRNA. MA410037 - JP 2018517429-A/79: FULLY STABILIZED ASYMMETRIC SIRNA. MA410036 - JP 2018517429-A/78: FULLY STABILIZED ASYMMETRIC SIRNA. MA410035 - JP 2018517429-A/77: FULLY STABILIZED ASYMMETRIC SIRNA. MA410092 - JP 2018517429-A/134: FULLY STABILIZED ASYMMETRIC SIRNA. MA410091 - JP 2018517429-A/133: FULLY STABILIZED ASYMMETRIC SIRNA. MA410033 - JP 2018517429-A/75: FULLY STABILIZED ASYMMETRIC SIRNA. MA410032 - JP 2018517429-A/74: FULLY STABILIZED ASYMMETRIC SIRNA. MA410090 - JP 2018517429-A/132: FULLY STABILIZED ASYMMETRIC SIRNA. MA410031 - JP 2018517429-A/73: FULLY STABILIZED ASYMMETRIC SIRNA. MA410089 - JP 2018517429-A/131: FULLY STABILIZED ASYMMETRIC SIRNA. MA410088 - JP 2018517429-A/130: FULLY STABILIZED ASYMMETRIC SIRNA. MA410030 - JP 2018517429-A/72: FULLY STABILIZED ASYMMETRIC SIRNA. MA410087 - JP 2018517429-A/129: FULLY STABILIZED ASYMMETRIC SIRNA. MA410027 - JP 2018517429-A/69: FULLY STABILIZED ASYMMETRIC SIRNA.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_no1Pathway - Actions of Nitric Oxide in the Heart h_vegfPathway - VEGF, Hypoxia, and Angiogenesis
Reactome (by CSHL, EBI, and GO)
Protein P17948 (Reactome details) participates in the following event(s):
R-HSA-194311 VEGFA,B,PLGF bind to VEGFR1 leading to receptor dimerization R-HSA-195418 NRP-2 associates with VEGFR1 forming complexes on cell surface R-HSA-195399 VEGF binds to VEGFR leading to receptor dimerization R-HSA-194306 Neurophilin interactions with VEGF and VEGFR R-HSA-194313 VEGF ligand-receptor interactions R-HSA-194138 Signaling by VEGF R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-162582 Signal Transduction