InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Flt1

Summary

InnateDB Protein

IDBP-209100.6

Last Modified

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

Gene Symbol

Flt1

Protein Name

FMS-like tyrosine kinase 1

Synonyms

AI323757; Flt-1; sFlt1; VEGFR-1; VEGFR1;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000031653

InnateDB Gene

IDBG-209098 (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, and proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts. 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 the 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, YES1 and PLCG, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 and PTK2/FAK1 (By similarity). {ECO:0000250}.

Subcellular Localization

Cell membrane; Single-pass type I membrane protein. Endosome {ECO:0000250}. Note=Autophosphorylation promotes ubiquitination and endocytosis. {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 15 experimentally validated interaction(s) in this database.
They are also associated with 22 interaction(s) predicted by orthology.

Experimentally validated
Total	15 [view]
Protein-Protein	14 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	22 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005021	vascular endothelial growth factor-activated receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
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
GO:0042802	identical protein binding

Biological Process

GO:0001525	angiogenesis
GO:0001569	patterning of blood vessels
GO:0002040	sprouting angiogenesis
GO:0002548	monocyte chemotaxis
GO:0006468	protein phosphorylation
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:0038084	vascular endothelial growth factor 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:0005634	nucleus
GO:0005768	endosome
GO:0005794	Golgi apparatus
GO:0005887	integral component of plasma membrane
GO:0043235	receptor complex

Protein Structure and Domains

PDB ID

MGI:95558

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR009135 Vascular endothelial growth factor receptor 1 (VEGFR1)
IPR011009 Protein kinase-like domain
IPR013098 Immunoglobulin I-set
IPR013106 Immunoglobulin V-set domain
IPR013151 Immunoglobulin
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF07679
PF07686
PF00047

PRINTS

PR00109
PR01833

PIRSF

SMART

SM00220
SM00408
SM00409
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt