InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: KDR

Summary

InnateDB Protein

IDBP-19165.6

Last Modified

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

Gene Symbol

KDR

Protein Name

kinase insert domain receptor (a type III receptor tyrosine kinase)

Synonyms

CD309; FLK1; VEGFR; VEGFR2;

Species

Homo sapiens

Ensembl Protein

ENSP00000263923

InnateDB Gene

IDBG-19161 (KDR)

Protein Structure

UniProt Annotation

Function

Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. {ECO:0000269PubMed:10102632, ECO:0000269PubMed:10368301, ECO:0000269PubMed:10600473, ECO:0000269PubMed:11387210, ECO:0000269PubMed:12649282, ECO:0000269PubMed:1417831, ECO:0000269PubMed:15026417, ECO:0000269PubMed:15215251, ECO:0000269PubMed:15962004, ECO:0000269PubMed:16966330, ECO:0000269PubMed:17303569, ECO:0000269PubMed:18529047, ECO:0000269PubMed:19668192, ECO:0000269PubMed:19834490, ECO:0000269PubMed:20080685, ECO:0000269PubMed:20224550, ECO:0000269PubMed:20705758, ECO:0000269PubMed:21893193, ECO:0000269PubMed:7929439, ECO:0000269PubMed:9160888, ECO:0000269PubMed:9804796, ECO:0000269PubMed:9837777}.

Subcellular Localization

Isoform 1: Cell membrane; Single-pass type I membrane protein. Cytoplasm. Nucleus. Cytoplasmic vesicle. Early endosome. Note=Detected on caveolae-enriched lipid rafts at the cell surface. Is recycled from the plasma membrane to endosomes and back again. Phosphorylation triggered by VEGFA binding promotes internalization and subsequent degradation. VEGFA binding triggers internalization and translocation to the nucleus.Cell junction {ECO:0000250}. Note=Localized with RAP1A at cell-cell junctions. {ECO:0000250}.Isoform 2: Secreted {ECO:0000305}.Isoform 3: Secreted.

Disease Associations

Hemangioma, capillary infantile (HCI) [MIM:602089]: A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring. {ECO:0000269PubMed:11807987, ECO:0000269PubMed:18931684}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Note=Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.

Tissue Specificity

Detected in cornea (at protein level). Widely expressed. {ECO:0000269PubMed:19668192}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 62 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	62 [view]
Protein-Protein	62 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0004716	receptor signaling protein tyrosine kinase activity
GO:0005021	vascular endothelial growth factor-activated receptor activity
GO:0005178	integrin binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019838	growth factor binding
GO:0038085	vascular endothelial growth factor binding
GO:0051879	Hsp90 protein binding

Biological Process

GO:0001525	angiogenesis
GO:0001541	ovarian follicle development
GO:0001570	vasculogenesis
GO:0001934	positive regulation of protein phosphorylation
GO:0001938	positive regulation of endothelial cell proliferation
GO:0001945	lymph vessel development
GO:0002042	cell migration involved in sprouting angiogenesis
GO:0002053	positive regulation of mesenchymal cell proliferation
GO:0003158	endothelium development
GO:0006468	protein phosphorylation
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0008284	positive regulation of cell proliferation
GO:0008360	regulation of cell shape
GO:0010595	positive regulation of endothelial cell migration
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0016032	viral process
GO:0016477	cell migration
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0023014	signal transduction by phosphorylation
GO:0030097	hemopoiesis
GO:0030198	extracellular matrix organization
GO:0030324	lung development
GO:0030335	positive regulation of cell migration
GO:0035162	embryonic hemopoiesis
GO:0035584	calcium-mediated signaling using intracellular calcium source
GO:0035924	cellular response to vascular endothelial growth factor stimulus
GO:0038083	peptidyl-tyrosine autophosphorylation
GO:0038084	vascular endothelial growth factor signaling pathway
GO:0043066	negative regulation of apoptotic process
GO:0043129	surfactant homeostasis
GO:0043410	positive regulation of MAPK cascade
GO:0045165	cell fate commitment
GO:0045446	endothelial cell differentiation
GO:0045766	positive regulation of angiogenesis
GO:0046777	protein autophosphorylation
GO:0048010	vascular endothelial growth factor receptor signaling pathway
GO:0048286	lung alveolus development
GO:0048469	cell maturation
GO:0048754	branching morphogenesis of an epithelial tube
GO:0050679	positive regulation of epithelial cell proliferation
GO:0050927	positive regulation of positive chemotaxis
GO:0051770	positive regulation of nitric-oxide synthase biosynthetic process
GO:0051894	positive regulation of focal adhesion assembly
GO:0055074	calcium ion homeostasis
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:2000352	negative regulation of endothelial cell apoptotic process
GO:2001214	positive regulation of vasculogenesis

Cellular Component

GO:0005576	extracellular region
GO:0005634	nucleus
GO:0005768	endosome
GO:0005769	early endosome
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009897	external side of plasma membrane
GO:0016023	cytoplasmic membrane-bounded vesicle
GO:0030054	cell junction
GO:0045121	membrane raft
GO:0071944	cell periphery
GO:0097443	sorting endosome

Protein Structure and Domains

PDB ID

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
IPR009136 Vascular endothelial growth factor receptor 2 (VEGFR2)
IPR011009 Protein kinase-like domain
IPR013098 Immunoglobulin I-set
IPR013106 Immunoglobulin V-set domain
IPR013151 Immunoglobulin
IPR013162 CD80-like, immunoglobulin C2-set
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF07679
PF07686
PF00047
PF08205

PRINTS

PR00109
PR01834

PIRSF

SMART

SM00220
SM00408
SM00409
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt