Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Kdr. (This text reflects annotations as of Thursday, July 24, 2014.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell protein tyrosine phosphatase, etc.. Mutations of this gene are implicated in infantile capillary hemangiomas. [provided by RefSeq, May 2009]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Kdr
  • participates in the following biological processes:
    • calcium ion homeostasis ^[14]
    • endothelial cell differentiation ^[25]
    • peptidyl-tyrosine autophosphorylation ^[11]
    • positive regulation of angiogenesis ^[22]
    • positive regulation of BMP signaling pathway ^[22]
    • vascular endothelial growth factor receptor signaling pathway ^[14]
    • vascular endothelial growth factor signaling pathway ^[14]
  • performs the following molecular functions:
    • vascular endothelial growth factor-activated receptor activity ^[14]
  • is located in the following cellular components:
    • cell junction ^[6]
    • cell periphery ^[20]
    • cell surface ^[13]
    • early endosome ^{[7, 11]}
    • external side of plasma membrane ^{[8, 18, 23]}
    • plasma membrane ^{[7, 11]}
    • sorting endosome ^[7]
• The gene product of Kdr has been shown to bind to the gene products of Flt4, Grem1, Met, Pdcl3, Plxna1, Tmem204. ^{[9, 11, 12, 16, 21, 24]} Researchers have inferred, based on physical interactions, that the gene product of Kdr
  • performs the following molecular functions:
    • growth factor binding ^{[4, 10]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Kdr
  • participates in the following biological processes:
    • branching morphogenesis of an epithelial tube ^[2]
    • cell fate commitment ^[3]
    • cell maturation ^[1]
    • cell migration involved in sprouting angiogenesis ^[11]
    • embryonic hemopoiesis ^[19]
    • endocardium development ^[19]
    • endothelium development ^[19]
    • hemopoiesis ^[17]
    • lung alveolus development ^[1]
    • lung development ^[2]
    • ovarian follicle development ^[15]
    • positive regulation of epithelial cell proliferation ^[2]
    • positive regulation of mesenchymal cell proliferation ^[2]
    • positive regulation of vasculogenesis ^[6]
    • surfactant homeostasis ^[1]
    • vasculogenesis ^{[17, 19]}
• Researchers have inferred, based on genetic interactions, that the gene product of Kdr
  • participates in the following biological processes:
    • cell migration based on interactions with Vegfa ^[5]
    • lymph vessel development based on interactions with Tmem204 ^[16]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Kdr:
  • participates in the following biological processes:
    • calcium-mediated signaling using intracellular calcium source
    • cellular response to vascular endothelial growth factor stimulus
    • endochondral bone growth
    • male gonad development
    • negative regulation of apoptotic process
    • negative regulation of endothelial cell apoptotic process
    • negative regulation of neuron apoptotic process
    • neuron projection morphogenesis
    • peptidyl-tyrosine phosphorylation
    • positive regulation of angiogenesis
    • positive regulation of calcium-mediated signaling
    • positive regulation of cell migration
    • positive regulation of cell proliferation
    • positive regulation of cytosolic calcium ion concentration
    • positive regulation of endothelial cell migration
    • positive regulation of endothelial cell proliferation
    • positive regulation of ERK1 and ERK2 cascade
    • positive regulation of focal adhesion assembly
    • positive regulation of long-term neuronal synaptic plasticity
    • positive regulation of MAPK cascade
    • positive regulation of nitric-oxide synthase biosynthetic process
    • positive regulation of phosphatidylinositol 3-kinase signaling
    • positive regulation of positive chemotaxis
    • positive regulation of protein phosphorylation
    • positive regulation of TOR signaling
    • positive regulation of vasodilation
    • protein autophosphorylation
    • regulation of cell shape
    • response to drug
    • response to hypoxia
    • vascular endothelial growth factor receptor signaling pathway
    • vascular endothelial growth factor signaling pathway
  • performs the following molecular functions:
    • growth factor binding
    • integrin binding
    • protein tyrosine kinase activity
    • vascular endothelial growth factor binding
    • vascular endothelial growth factor-activated receptor activity
  • is located in the following cellular components:
    • cytoplasm
    • endosome
    • Golgi apparatus
    • integral component of plasma membrane
    • membrane raft
    • neuron projection
    • neuronal cell body
    • plasma membrane

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Summary text based on GO annotations supported by structural data

• Kdr encodes a protein or proteins that contain the following InterPro domains: Immunoglobulin I-set, Immunoglobulin subtype, Immunoglobulin subtype 2, Immunoglobulin V-set, Immunoglobulin-like domain, Immunoglobulin-like fold, Protein kinase, ATP binding site, Protein kinase, catalytic domain, Protein kinase-like domain, Serine-threonine/tyrosine-protein kinase catalytic domain, Tyrosine-protein kinase, active site, Tyrosine-protein kinase, catalytic domain, Tyrosine-protein kinase, receptor class III, conserved site, Tyrosine-protein kinase, vascular endothelial growth factor receptor 2 (VEGFR2), indicating that the gene product:
  • participates in the following biological processes:
    • protein phosphorylation
    • transmembrane receptor protein tyrosine kinase signaling pathway
  • performs the following molecular functions:
    • ATP binding
    • protein kinase activity
    • transferase activity, transferring phosphorus-containing groups
    • transmembrane receptor protein tyrosine kinase activity
  • is located in the following cellular components:
    • integral component of membrane
    • membrane

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Kdr indicates that it:
  • participates in the following biological processes:
    • angiogenesis
    • cell differentiation
    • multicellular organismal development
    • phosphorylation
  • performs the following molecular functions:
    • ATP binding
    • kinase activity
    • nucleotide binding
    • transferase activity
  • is located in the following cellular components:
    • cytoplasmic vesicle
    • extracellular region
    • integral component of membrane
    • membrane
    • nucleus
• Kdr has been associated with the Enzyme Commission numbers: 2.7.10.1, which implies that the gene product:
  • performs the following molecular functions:
    • transmembrane receptor protein tyrosine kinase activity

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References

1. Compernolle V et al. (2002) Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med, 8:702-10. (PubMed:12053176)
2. Del Moral PM et al. (2006) VEGF-A signaling through Flk-1 is a critical facilitator of early embryonic lung epithelial to endothelial crosstalk and branching morphogenesis. Dev Biol, 290:177-88. (PubMed:16375885)
3. Ema M et al. (2003) Combinatorial effects of Flk1 and Tal1 on vascular and hematopoietic development in the mouse. Genes Dev, 17:380-93. (PubMed:12569129)
4. Halder JB et al. (2000) Differential expression of VEGF isoforms and VEGF(164)-specific receptor neuropilin-1 in the mouse uterus suggests a role for VEGF(164) in vascular permeability and angiogenesis during implantation. Genesis, 26:213-24. (PubMed:10705382)
5. Hiratsuka S et al. (2005) Vascular endothelial growth factor A (VEGF-A) is involved in guidance of VEGF receptor-positive cells to the anterior portion of early embryos. Mol Cell Biol, 25:355-63. (PubMed:15601856)
6. Kanemura H et al. (2009) Impaired vascular development in the yolk sac and allantois in mice lacking RA-GEF-1. Biochem Biophys Res Commun, 387:754-9. (PubMed:19635461)
7. Lanahan A et al. (2013) The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis. Dev Cell, 25:156-68. (PubMed:23639442)
8. Lee D et al. (2008) ER71 acts downstream of BMP, Notch, and Wnt signaling in blood and vessel progenitor specification. Cell Stem Cell, 2:497-507. (PubMed:18462699)
9. Lu KV et al. (2012) VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex. Cancer Cell, 22:21-35. (PubMed:22789536)
10. Millauer B et al. (1993) High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell, 72:835-46. (PubMed:7681362)
11. Mitola S et al. (2010) Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2. Blood, 116:3677-80. (PubMed:20660291)
12. Nilsson I et al. (2010) VEGF receptor 2/-3 heterodimers detected in situ by proximity ligation on angiogenic sprouts. EMBO J, 29:1377-88. (PubMed:20224550)
13. Pereira LA et al. (2012) Pdgfralpha and Flk1 are direct target genes of Mixl1 in differentiating embryonic stem cells. Stem Cell Res, 8:165-79. (PubMed:22265737)
14. Quinn TP et al. (1993) Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci U S A, 90:7533-7. (PubMed:8356051)
15. Roberts AE et al. (2007) Neutralization of endogenous vascular endothelial growth factor depletes primordial follicles in the mouse ovary. Biol Reprod, 76:218-23. (PubMed:17050862)
16. Saharinen P et al. (2010) Claudin-like protein 24 interacts with the VEGFR-2 and VEGFR-3 pathways and regulates lymphatic vessel development. Genes Dev, 24:875-80. (PubMed:20439428)
17. Sakurai Y et al. (2005) Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice. Proc Natl Acad Sci U S A, 102:1076-81. (PubMed:15644447)
18. Serrano AG et al. (2010) Contrasting effects of Sox17- and Sox18-sustained expression at the onset of blood specification. Blood, 115:3895-8. (PubMed:20228271)
19. Shalaby F et al. (1995) Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature, 376:62-6. (PubMed:7596435)
20. Siva K et al. (2006) Rudhira is a cytoplasmic WD40 protein expressed in mouse embryonic stem cells and during embryonic erythropoiesis. Gene Expr Patterns, 6:225-34. (PubMed:16099728)
21. Srinivasan S et al. (2013) Identification of PDCL3 as a novel chaperone protein involved in the generation of functional VEGF receptor 2. J Biol Chem, 288:23171-81. (PubMed:23792958)
22. Suzuki Y et al. (2010) BMP-9 induces proliferation of multiple types of endothelial cells in vitro and in vivo. J Cell Sci, 123:1684-92. (PubMed:20406889)
23. Takayanagi S et al. (2006) Genetic marking of hematopoietic stem and endothelial cells: identification of the Tmtsp gene encoding a novel cell surface protein with the thrombospondin-1 domain. Blood, 107:4317-25. (PubMed:16455951)
24. Toyofuku T et al. (2004) Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2. Genes Dev, 18:435-47. (PubMed:14977921)
25. Wu Y et al. (2003) HoxB5 is an upstream transcriptional switch for differentiation of the vascular endothelium from precursor cells. Mol Cell Biol, 23:5680-91. (PubMed:12897140)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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