InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FLT1

Summary

InnateDB Protein

IDBP-595661.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

FLT1

Protein Name

fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)

Synonyms

FLT; FLT-1; VEGFR-1; VEGFR1;

Species

Homo sapiens

Ensembl Protein

ENSP00000437631

InnateDB Gene

IDBG-20108 (FLT1)

Protein Structure

UniProt Annotation

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}.

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}.

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.

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}.

Comments

Interactions

Number of Interactions

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]
Protein-Protein	31 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	8 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0005021	vascular endothelial growth factor-activated receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0019838	growth factor binding
GO:0036326	VEGF-A-activated receptor activity
GO:0036327	VEGF-B-activated receptor activity
GO:0036332	placental growth factor-activated receptor activity

Biological Process

GO:0002548	monocyte chemotaxis
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0008284	positive regulation of cell proliferation
GO:0010863	positive regulation of phospholipase C activity
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0016477	cell migration
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030154	cell differentiation
GO:0030335	positive regulation of cell migration
GO:0030949	positive regulation of vascular endothelial growth factor receptor signaling pathway
GO:0035924	cellular response to vascular endothelial growth factor stimulus
GO:0036323	vascular endothelial growth factor receptor-1 signaling pathway
GO:0043406	positive regulation of MAP kinase activity
GO:0043410	positive regulation of MAPK cascade
GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity
GO:0045766	positive regulation of angiogenesis
GO:0046777	protein autophosphorylation
GO:0048010	vascular endothelial growth factor receptor signaling pathway
GO:0048514	blood vessel morphogenesis
GO:0048598	embryonic morphogenesis

Cellular Component

GO:0005615	extracellular space
GO:0005768	endosome
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0043235	receptor complex

Protein Structure and Domains

PDB ID

InterPro

IPR003596 Immunoglobulin V-set, subgroup
IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR009135 Vascular endothelial growth factor receptor 1 (VEGFR1)
IPR013098 Immunoglobulin I-set
IPR013106 Immunoglobulin V-set domain

PFAM

PF07679
PF07686

PRINTS

PR01833

PIRSF

SMART

SM00406
SM00408
SM00409

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt