Kinase insert domain receptor

Protein-coding gene in the species Homo sapiens
KDR
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1VR2, 1Y6A, 1Y6B, 1YWN, 2M59, 2MET, 2MEU, 2OH4, 2P2H, 2P2I, 2QU5, 2QU6, 2RL5, 2X1W, 2X1X, 2XIR, 3B8Q, 3B8R, 3BE2, 3C7Q, 3CJF, 3CJG, 3CP9, 3CPB, 3CPC, 3DTW, 3EFL, 3EWH, 3KVQ, 3S35, 3S36, 3S37, 3U6J, 3VHE, 3VHK, 3VID, 3VNT, 3VO3, 3WZD, 3WZE, 4AG8, 4AGC, 4AGD, 4ASD, 4ASE, 5EW3

Identifiers
AliasesKDR, CD309, FLK1, VEGFR, VEGFR2, Kinase insert domain receptor
External IDsOMIM: 191306; MGI: 96683; HomoloGene: 55639; GeneCards: KDR; OMA:KDR - orthologs
Gene location (Human)
Chromosome 4 (human)
Chr.Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for KDR
Genomic location for KDR
Band4q12Start55,078,481 bp[1]
End55,125,595 bp[1]
Gene location (Mouse)
Chromosome 5 (mouse)
Chr.Chromosome 5 (mouse)[2]
Chromosome 5 (mouse)
Genomic location for KDR
Genomic location for KDR
Band5 C3.3|5 40.23 cMStart76,093,487 bp[2]
End76,139,118 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • germinal epithelium

  • lower lobe of lung

  • parietal pleura

  • pericardium

  • right lobe of thyroid gland

  • right lung

  • left lobe of thyroid gland

  • upper lobe of lung

  • visceral pleura

  • upper lobe of left lung
Top expressed in
  • vein

  • left lung

  • left lung lobe

  • right lung

  • right lung lobe

  • ankle joint

  • cardiac muscles

  • vascular endothelium

  • brown adipose tissue

  • utricle
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • transferase activity
  • Hsp90 protein binding
  • nucleotide binding
  • protein kinase activity
  • growth factor binding
  • vascular endothelial growth factor binding
  • kinase activity
  • integrin binding
  • protein binding
  • ATP binding
  • transmembrane receptor protein tyrosine kinase activity
  • vascular endothelial growth factor-activated receptor activity
  • protein tyrosine kinase activity
  • identical protein binding
  • receptor tyrosine kinase
  • transmembrane signaling receptor activity
  • cadherin binding
Cellular component
  • cytoplasm
  • integral component of membrane
  • Golgi apparatus
  • membrane
  • integral component of plasma membrane
  • extracellular region
  • cell junction
  • early endosome
  • membrane raft
  • sorting endosome
  • cytoplasmic vesicle
  • nucleus
  • endosome
  • plasma membrane
  • endoplasmic reticulum
  • receptor complex
Biological process
  • negative regulation of endothelial cell apoptotic process
  • cell differentiation
  • positive regulation of protein phosphorylation
  • positive regulation of mitochondrial fission
  • positive regulation of endothelial cell proliferation
  • phosphorylation
  • extracellular matrix organization
  • negative regulation of apoptotic process
  • positive regulation of nitric-oxide synthase biosynthetic process
  • cell migration involved in sprouting angiogenesis
  • positive regulation of angiogenesis
  • vasculogenesis
  • positive regulation of endothelial cell migration
  • multicellular organism development
  • protein phosphorylation
  • positive regulation of macroautophagy
  • positive regulation of mitochondrial depolarization
  • positive regulation of vasculogenesis
  • embryonic hemopoiesis
  • endothelium development
  • regulation of cell shape
  • positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway
  • positive regulation of ERK1 and ERK2 cascade
  • peptidyl-tyrosine autophosphorylation
  • protein autophosphorylation
  • positive regulation of focal adhesion assembly
  • positive regulation of phosphatidylinositol 3-kinase signaling
  • peptidyl-tyrosine phosphorylation
  • cellular response to vascular endothelial growth factor stimulus
  • viral process
  • calcium-mediated signaling using intracellular calcium source
  • positive regulation of MAPK cascade
  • positive regulation of positive chemotaxis
  • transmembrane receptor protein tyrosine kinase signaling pathway
  • vascular endothelial growth factor receptor signaling pathway
  • positive regulation of cell population proliferation
  • angiogenesis
  • positive regulation of cell migration
  • protein kinase B signaling
  • ERK1 and ERK2 cascade
  • negative regulation of gene expression
  • positive regulation of blood vessel endothelial cell migration
  • cellular response to hydrogen sulfide
  • positive regulation of cell migration involved in sprouting angiogenesis
  • negative regulation of signal transduction
  • sprouting angiogenesis
  • cell migration
  • endothelial cell differentiation
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

3791

16542

Ensembl

ENSG00000128052

ENSMUSG00000062960

UniProt

P35968

P35918
Q8VCD0

RefSeq (mRNA)

NM_002253

NM_010612
NM_001363216

RefSeq (protein)

NP_002244

NP_034742
NP_001350145

Location (UCSC)Chr 4: 55.08 – 55.13 MbChr 5: 76.09 – 76.14 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Kinase insert domain receptor (KDR, a type IV receptor tyrosine kinase) also known as vascular endothelial growth factor receptor 2 (VEGFR-2) is a VEGF receptor. KDR is the human gene encoding it. KDR has also been designated as CD309 (cluster of differentiation 309). KDR is also known as Flk1 (Fetal Liver Kinase 1).

The Q472H germline KDR genetic variant affects VEGFR-2 phosphorylation and has been found to associate with microvessel density in NSCLC.[5]

Interactions

Kinase insert domain receptor has been shown to interact with SHC2,[6] Annexin A5[7] and SHC1.[8][9]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000128052 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000062960 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Glubb DM, Cerri E, Giese A, Zhang W, Mirza O, Thompson EE, Chen P, Das S, Jassem J, Rzyman W, Lingen MW, Salgia R, Hirsch FR, Dziadziuszko R, Ballmer-Hofer K, Innocenti F (August 2011). "Novel functional germline variants in the VEGF receptor 2 gene and their effect on gene expression and microvessel density in lung cancer". Clinical Cancer Research. 17 (16): 5257–67. doi:10.1158/1078-0432.CCR-11-0379. PMC 3156871. PMID 21712447.
  6. ^ Warner AJ, Lopez-Dee J, Knight EL, Feramisco JR, Prigent SA (April 2000). "The Shc-related adaptor protein, Sck, forms a complex with the vascular-endothelial-growth-factor receptor KDR in transfected cells". The Biochemical Journal. 347 (Pt 2): 501–9. doi:10.1042/0264-6021:3470501. PMC 1220983. PMID 10749680.
  7. ^ Wen Y, Edelman JL, Kang T, Sachs G (May 1999). "Lipocortin V may function as a signaling protein for vascular endothelial growth factor receptor-2/Flk-1". Biochemical and Biophysical Research Communications. 258 (3): 713–21. doi:10.1006/bbrc.1999.0678. PMID 10329451.
  8. ^ Zanetti A, Lampugnani MG, Balconi G, Breviario F, Corada M, Lanfrancone L, Dejana E (April 2002). "Vascular endothelial growth factor induces SHC association with vascular endothelial cadherin: a potential feedback mechanism to control vascular endothelial growth factor receptor-2 signaling". Arteriosclerosis, Thrombosis, and Vascular Biology. 22 (4): 617–22. doi:10.1161/01.ATV.0000012268.84961.AD. PMID 11950700.
  9. ^ D'Angelo G, Martini JF, Iiri T, Fantl WJ, Martial J, Weiner RI (May 1999). "16K human prolactin inhibits vascular endothelial growth factor-induced activation of Ras in capillary endothelial cells". Molecular Endocrinology. 13 (5): 692–704. doi:10.1210/mend.13.5.0280. PMID 10319320.

Further reading

  • Holmes K, Roberts OL, Thomas AM, Cross MJ (October 2007). "Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition". Cellular Signalling. 19 (10): 2003–12. doi:10.1016/j.cellsig.2007.05.013. PMID 17658244.
  • Petrova TV, Makinen T, Alitalo K (November 1999). "Signaling via vascular endothelial growth factor receptors". Experimental Cell Research. 253 (1): 117–30. doi:10.1006/excr.1999.4707. PMID 10579917.
  • Wang J, Fu X, Jiang C, Yu L, Wang M, Han W, Liu L, Wang J (May 2014). "Bone marrow mononuclear cell transplantation promotes therapeutic angiogenesis via upregulation of the VEGF-VEGFR2 signaling pathway in a rat model of vascular dementia". Behavioural Brain Research. 265: 171–80. doi:10.1016/j.bbr.2014.02.033. PMC 4000455. PMID 24589546.
  • Sato Y, Kanno S, Oda N, Abe M, Ito M, Shitara K, Shibuya M (May 2000). "Properties of two VEGF receptors, Flt-1 and KDR, in signal transduction". Annals of the New York Academy of Sciences. 902 (1): 201–5, discussion 205–7. Bibcode:2000NYASA.902..201S. doi:10.1111/j.1749-6632.2000.tb06314.x. PMID 10865839. S2CID 11488629.
  • Zachary I, Gliki G (February 2001). "Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family". Cardiovascular Research. 49 (3): 568–81. doi:10.1016/S0008-6363(00)00268-6. PMID 11166270.
  • Vené R, Benelli R, Noonan DM, Albini A (2001). "HIV-Tat dependent chemotaxis and invasion, key aspects of tat mediated pathogenesis". Clinical & Experimental Metastasis. 18 (7): 533–8. doi:10.1023/A:1011991906685. PMID 11688957. S2CID 24787929.
  • Lenton K (2003). "VEGFR-2 (KDR/Flk-1)". Journal of Biological Regulators and Homeostatic Agents. 16 (3): 227–32. PMID 12456025.
  • Matsumoto T, Mugishima H (June 2006). "Signal transduction via vascular endothelial growth factor (VEGF) receptors and their roles in atherogenesis". Journal of Atherosclerosis and Thrombosis. 13 (3): 130–5. doi:10.5551/jat.13.130. PMID 16835467.

External links

  • Kinase+insert+domain+receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  • Overview of all the structural information available in the PDB for UniProt: P35968 (Vascular endothelial growth factor receptor 2) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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  • 1y6a: Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor
    1y6a: Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor
  • 1y6b: Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor
    1y6b: Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor
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