Kinase insert domain receptor

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).

KDR
Available structures PDB Ortholog 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
Aliases	KDR, CD309, FLK1, VEGFR, VEGFR2, Kinase insert domain receptor
External IDs	OMIM: 191306 MGI: 96683 HomoloGene: 55639 GeneCards: KDR
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q12 Start 55,078,481 bp[1] End 55,125,595 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 C3.3|5 40.23 cM Start 75,932,827 bp[2] End 75,978,458 bp[2]
RNA expression pattern 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 • GO:0001948 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 • cell nucleus • endosome • cell 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 • 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 • GO:0022415 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 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
Species	Human	Mouse
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 Mb	Chr 5: 75.93 – 75.98 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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

• Cluster of differentiation
• VEGF receptors

References

1. GRCh38: Ensembl release 89: ENSG00000128052 - Ensembl, May 2017
2. 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" (PDF). 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.
• 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.
• 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 US 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.