KDR

KDR
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	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
Identifikatori
Aliasi	KDR
Vanjski ID-jevi	OMIM: 191306 MGI: 96683 HomoloGene: 55639 GeneCards: KDR
Lokacija gena (čovjek)
Hrom.	Hromosom 4 (čovjek)
Kraj	55,125,595 bp
Lokacija gena (miš)
Hrom.	Hromosom 5 (miš)
Kraj	76,139,118 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• aktivnost sa transferazom; • Hsp90 protein binding; • nucleotide binding; • protein kinase activity; • growth factor binding; • vascular endothelial growth factor binding; • kinase activity; • integrin binding; • GO:0001948, GO:0016582 vezivanje za proteine; • ATP binding; • transmembrane receptor protein tyrosine kinase activity; • vascular endothelial growth factor-activated receptor activity; • protein tyrosine kinase activity; • vezivanje identičnih proteina; • Receptorska tirozin-kinaza; • transmembrane signaling receptor activity; • cadherin binding;
Ćelijska komponenta	• citoplazma; • integral component of membrane; • Golđijev aparat; • membrana; • integral component of plasma membrane; • extracellular region; • međućelijske veze; • early endosome; • Lipidni splav; • sorting endosome; • GO:0016023 citoplazmatska vezikula; • jedro; • endozom; • ćelijska membrana; • Endoplazmatski retikulum; • receptor complex;
Biološki proces	• negative regulation of endothelial cell apoptotic process; • Ćelijska diferencijacija; • positive regulation of protein phosphorylation; • positive regulation of mitochondrial fission; • positive regulation of endothelial cell proliferation; • Fosforilacija; • 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; • Vaskulogeneza; • 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; • 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 population proliferation; • Angiogeneza; • 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; • Ćelijska migracija; • endothelial cell differentiation;
	Izvori:Amigo / QuickGO
Ortolozi
	3791
	16542
	ENSG00000128052
	ENSMUSG00000062960
	P35968
	P35918; Q8VCD0
	NM_002253
	NM_010612; NM_001363216
	NP_002244
	NP_034742; NP_001350145
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Receptor domena kinazne insercije (KDR, tip IV receptora tirozin-kinaza), znan i kao receptor 2 vaskularnog endotelnog faktora rasta (VEGFR-2) jest VEGF-receptor koji je kod ljudi kodiran genom KDR sa hromosoma 4. Označava se i kao CD309 (klaster diferencijacije 309) i kao Flk1 (eng. Fetal Liver Kinase 1 = fetusna jetrena kinaza).

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.356 aminokiselina, а molekulska težina 151.527 Da.^[5]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MQSKVLLAVA	LWLCVETRAA	SVGLPSVSLD	LPRLSIQKDI	LTIKANTTLQ
ITCRGQRDLD	WLWPNNQSGS	EQRVEVTECS	DGLFCKTLTI	PKVIGNDTGA
YKCFYRETDL	ASVIYVYVQD	YRSPFIASVS	DQHGVVYITE	NKNKTVVIPC
LGSISNLNVS	LCARYPEKRF	VPDGNRISWD	SKKGFTIPSY	MISYAGMVFC
EAKINDESYQ	SIMYIVVVVG	YRIYDVVLSP	SHGIELSVGE	KLVLNCTART
ELNVGIDFNW	EYPSSKHQHK	KLVNRDLKTQ	SGSEMKKFLS	TLTIDGVTRS
DQGLYTCAAS	SGLMTKKNST	FVRVHEKPFV	AFGSGMESLV	EATVGERVRI
PAKYLGYPPP	EIKWYKNGIP	LESNHTIKAG	HVLTIMEVSE	RDTGNYTVIL
TNPISKEKQS	HVVSLVVYVP	PQIGEKSLIS	PVDSYQYGTT	QTLTCTVYAI
PPPHHIHWYW	QLEEECANEP	SQAVSVTNPY	PCEEWRSVED	FQGGNKIEVN
KNQFALIEGK	NKTVSTLVIQ	AANVSALYKC	EAVNKVGRGE	RVISFHVTRG
PEITLQPDMQ	PTEQESVSLW	CTADRSTFEN	LTWYKLGPQP	LPIHVGELPT
PVCKNLDTLW	KLNATMFSNS	TNDILIMELK	NASLQDQGDY	VCLAQDRKTK
KRHCVVRQLT	VLERVAPTIT	GNLENQTTSI	GESIEVSCTA	SGNPPPQIMW
FKDNETLVED	SGIVLKDGNR	NLTIRRVRKE	DEGLYTCQAC	SVLGCAKVEA
FFIIEGAQEK	TNLEIIILVG	TAVIAMFFWL	LLVIILRTVK	RANGGELKTG
YLSIVMDPDE	LPLDEHCERL	PYDASKWEFP	RDRLKLGKPL	GRGAFGQVIE
ADAFGIDKTA	TCRTVAVKML	KEGATHSEHR	ALMSELKILI	HIGHHLNVVN
LLGACTKPGG	PLMVIVEFCK	FGNLSTYLRS	KRNEFVPYKT	KGARFRQGKD
YVGAIPVDLK	RRLDSITSSQ	SSASSGFVEE	KSLSDVEEEE	APEDLYKDFL
TLEHLICYSF	QVAKGMEFLA	SRKCIHRDLA	ARNILLSEKN	VVKICDFGLA
RDIYKDPDYV	RKGDARLPLK	WMAPETIFDR	VYTIQSDVWS	FGVLLWEIFS
LGASPYPGVK	IDEEFCRRLK	EGTRMRAPDY	TTPEMYQTML	DCWHGEPSQR
PTFSELVEHL	GNLLQANAQQ	DGKDYIVLPI	SETLSMEEDS	GLSLPTSPVS
CMEEEEVCDP	KFHYDNTAGI	SQYLQNSKRK	SRPVSVKTFE	DIPLEEPEVK
VIPDDNQTDS	GMVLASEELK	TLEDRTKLSP	SFGGMVPSKS	RESVASEGSN
QTSGYQSGYH	SDDTDTTVYS	SEEAELLKLI	EIGVQTGSTA	QILQPDSGTT
LSSPPV

Funkcija

Genetička varijanta Q472H zametne linije KDR utiče na fosforilaciju VEGFR-2 i utvrđeno je da je povezana sa gustoćom mikrovaskularnih sudova u karcinomu pluća nemalih ćelija (NSCLC).^[6]

Interakcije

Pokazalo se da receptor domen insercije kinaze ima interakcije sa SHC2,^[7] aneksinom A5^[8] i SHC1.^[9]^[10]

Također pogledajte

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000128052 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000062960 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "UniProt, P35968" (jezik: engleski). Pristupljeno 29. 10. 2021.
^ 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.
^ 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.
^ Wen Y, Edelman JL, Kang T, Sachs G (maj 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.
^ 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.
^ D'Angelo G, Martini JF, Iiri T, Fantl WJ, Martial J, Weiner RI (maj 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.

Dopunska literatura

Holmes K, Roberts OL, Thomas AM, Cross MJ (oktobar 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 (novembar 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 (maj 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 (maj 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 (februar 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 (juni 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.