FLT1 - Vascular endothelial growth factor receptor 1 - human protein (Function)
 
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FLT1 »  Vascular endothelial growth factor receptor 1   [ EC 2.7.10.1 ]  (VEGFR-1)
 
Protein also known as:  Vascular permeability factor receptor.
Gene name:  FLT1
Entry whose protein(s) existence is based on evidence at protein level
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1 440 8
GENE REF ISO

Function

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Overview 
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.  
18
  • CuratedUniProtKB
Isoform  Iso 7   Has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.  
18
  • CuratedUniProtKB
Isoform  Iso 1   Phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1.  
18
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Growth factor bindingdefinition[GO:0019838]  
5
  • IPIUniProtKB
  • IPIBHF-UCL
Identical protein bindingdefinition[GO:0042802] silver  
  • IEAOrtholog Compara
Placental growth factor-activated receptor activitydefinition[GO:0036332]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
10
  • IPIIntAct
Transmembrane receptor protein tyrosine kinase activitydefinition[GO:0004714]  
1
  • TASPINC
Vascular endothelial growth factor-activated receptor activitydefinition[GO:0005021]  
3
  • IMPUniProtKB
  • IDABHF-UCL
VEGF-A-activated receptor activitydefinition[GO:0036326]  
1
  • IDAUniProtKB
VEGF-B-activated receptor activitydefinition[GO:0036327]  
1
  • IDAUniProtKB
GO biological process 
Blood vessel morphogenesisdefinition[GO:0048514]  
  • ISSOrtholog Curator
Cell differentiationdefinition[GO:0030154]  
  • IEAUniProtKB KW
Cell migrationdefinition[GO:0016477]  
1
  • IMPUniProtKB
Cellular response to vascular endothelial growth factor stimulusdefinition[GO:0035924]  
1
  • IDAUniProtKB
Embryonic morphogenesisdefinition[GO:0048598]  
  • ISSOrtholog Curator
Monocyte chemotaxisdefinition[GO:0002548]  
2
  • IDAUniProtKB
Patterning of blood vesselsdefinition[GO:0001569] silver  
  • IEAOrtholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
2
  • IDAUniProtKB
Positive regulation of angiogenesisdefinition[GO:0045766]  
1
  • IMPUniProtKB
Positive regulation of cell migrationdefinition[GO:0030335]  
1
  • IDAUniProtKB
Positive regulation of cell proliferationdefinition[GO:0008284]  
1
  • TASPINC
Positive regulation of MAP kinase activitydefinition[GO:0043406]  
1
  • IDAUniProtKB
Positive regulation of MAPK cascadedefinition[GO:0043410]  
1
  • IDAUniProtKB
Positive regulation of phosphatidylinositol 3-kinase activitydefinition[GO:0043552]  
1
  • IMPUniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014068]  
1
  • IMPUniProtKB
Positive regulation of phospholipase C activitydefinition[GO:0010863]  
1
  • IMPUniProtKB
Positive regulation of vascular endothelial growth factor receptor signaling pathwaydefinition[GO:0030949]  
1
  • IDABHF-UCL
Protein autophosphorylationdefinition[GO:0046777]  
2
  • IDAUniProtKB
Sprouting angiogenesisdefinition[GO:0002040] silver  
  • IEAOrtholog Compara
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169]  
1
  • TASPINC
Vascular endothelial growth factor receptor signaling pathwaydefinition[GO:0048010]  
2
  • IMPUniProtKB
Vascular endothelial growth factor receptor-1 signaling pathwaydefinition[GO:0036323]  
1
  • IDAUniProtKB
Vascular endothelial growth factor signaling pathwaydefinition[GO:0038084] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
5
  • CuratedUniProtKB
It is regulated in the following manner
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.  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Cytokine-cytokine receptor interaction  hsa04060+2321  
Endocytosis  hsa04144+2321  
Focal adhesion  hsa04510+2321  
Rheumatoid arthritis  hsa05323+2321  
According to Reactome, this protein belongs to the following pathways:
Neurophilin interactions with VEGF and VEGFR  REACT_12473  
VEGF binds to VEGFR leading to receptor dimerization  REACT_12583  
 

Keywords

Biological process 
Angiogenesis  definition   [KW-0037]
Chemotaxis  definition   [KW-0145]
Differentiation  definition   [KW-0221]
Molecular function 
Developmental protein  definition   [KW-0217]
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: FLT1
GenomeRNAi: 2321
PRO: PR:P17948
Chemistry
GuidetoPHARMACOLOGY: 1812