InnateDB Protein
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IDBP-589838.3
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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FLT1
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Protein Name
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fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)
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Synonyms
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FLT; FLT-1; VEGFR-1; VEGFR1;
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000443311
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InnateDB Gene
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IDBG-20108 (FLT1)
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Protein Structure
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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. {ECO:0000269PubMed:11141500, ECO:0000269PubMed:11312102, ECO:0000269PubMed:11811792, ECO:0000269PubMed:12796773, ECO:0000269PubMed:14633857, ECO:0000269PubMed:15735759, ECO:0000269PubMed:16685275, ECO:0000269PubMed:18079407, ECO:0000269PubMed:18515749, ECO:0000269PubMed:18583712, ECO:0000269PubMed:18593464, ECO:0000269PubMed:20512933, ECO:0000269PubMed:20551949, ECO:0000269PubMed:21752276, ECO:0000269PubMed:7824266, ECO:0000269PubMed:8248162, ECO:0000269PubMed:8605350, ECO:0000269PubMed:9299537}.
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Subcellular Localization |
Isoform 1: Cell membrane; Single-pass type I membrane protein. Endosome. Note=Autophosphorylation promotes ubiquitination and endocytosis.Isoform 2: Secreted {ECO:0000269PubMed:8248162}.Isoform 3: Secreted.Isoform 4: Secreted.Isoform 5: Cytoplasm {ECO:0000305}.Isoform 6: Cytoplasm {ECO:0000305}.Isoform 7: Cytoplasm {ECO:0000305}.
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Disease Associations |
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.Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.
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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). {ECO:0000269PubMed:18515749, ECO:0000269PubMed:20512933}.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 31 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.
Experimentally validated |
Total |
31
[view]
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Protein-Protein |
31
[view]
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Protein-DNA |
0
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Predicted by orthology |
Total |
8 [view]
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Molecular Function |
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Biological Process |
GO:0002548
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monocyte chemotaxis
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GO:0007169
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transmembrane receptor protein tyrosine kinase signaling pathway
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GO:0008284
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positive regulation of cell proliferation
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GO:0010863
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positive regulation of phospholipase C activity
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GO:0014068
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positive regulation of phosphatidylinositol 3-kinase signaling
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GO:0016477
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cell migration
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GO:0018108
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peptidyl-tyrosine phosphorylation
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GO:0030154
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cell differentiation
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GO:0030335
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positive regulation of cell migration
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GO:0030949
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positive regulation of vascular endothelial growth factor receptor signaling pathway
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GO:0035924
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cellular response to vascular endothelial growth factor stimulus
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GO:0036323
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vascular endothelial growth factor receptor-1 signaling pathway
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GO:0043406
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positive regulation of MAP kinase activity
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GO:0043410
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positive regulation of MAPK cascade
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GO:0043552
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positive regulation of phosphatidylinositol 3-kinase activity
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GO:0045766
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positive regulation of angiogenesis
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GO:0046777
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protein autophosphorylation
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GO:0048010
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vascular endothelial growth factor receptor signaling pathway
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GO:0048514
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blood vessel morphogenesis
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GO:0048598
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embryonic morphogenesis
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Cellular Component |
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PDB ID |
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InterPro |
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PFAM |
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PRINTS |
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PIRSF |
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SMART |
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TIGRFAMs |
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Modification |
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SwissProt |
P17948
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PhosphoSite |
PhosphoSite-P17948
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TrEMBL |
H9N1E8
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UniProt Splice Variant |
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Entrez Gene |
2321
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UniGene |
Hs.658796
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RefSeq |
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HUGO |
HGNC:3763
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OMIM |
165070
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CCDS |
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HPRD |
01297
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IMGT |
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EMBL |
AF063657
AK292936
AK300392
AL138712
AL139005
BC039007
CH471075
D00133
DQ836394
DQ836395
DQ836396
EF491868
EF491869
EF491870
EU332841
EU360600
EU368830
EU826561
JF509745
U01134
X51602
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GenPept |
AAC16449
AAC50060
AAH39007
ABI53803
ABI53804
ABI53805
ABS32268
ABS32269
ABS32270
ABY87530
ACA62948
ACB05747
ACF47597
AFC77955
BAA00080
BAF85625
BAG62125
CAA35946
CAI14846
CAI17096
EAX08431
EAX08432
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