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Kinase insert domain receptor

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From Wikipedia, the free encyclopedia

Protein-coding gene in the species Homo sapiens

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;OMA:KDR - orthologs

Gene location (Human)

Chr.	Chromosome 4 (human)^[1]

Band	4q12	Start	55,078,481bp^[1]
Band	4q12	End	55,125,595bp^[1]

Gene location (Mouse)

Chr.	Chromosome 5 (mouse)^[2]

Band	5 C3.3\|5 40.23 cM	Start	76,093,487bp^[2]
Band	5 C3.3\|5 40.23 cM	End	76,139,118bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

germinal epithelium

lower lobe of lung

parietal pleura

pericardium

decidua

right lobe of thyroid gland

right lung

body of uterus

left lobe of thyroid gland

upper lobe of lung

Top expressed in

vasculature of trunk

Vasculature of brain

vein

dorsal aorta

left lung

left lung lobe

right lung

endothelial cell of lymphatic vessel

right lung lobe

neural layer of retina

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

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: 76.09 – 76.14 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Kinase insert domain receptor (KDR, a type IV receptor tyrosine kinase) also known asvascular endothelial growth factor receptor 2 (VEGFR-2) is aVEGF receptor.KDR is the humangene encoding it. KDR has also been designated asCD309 (cluster of differentiation 309). KDR is also known as Flk1 (Fetal Liver Kinase 1).

The Q472H germlineKDR genetic variant affects VEGFR-2 phosphorylation and has been found to associate with microvessel density inNSCLC.^[5]

Interactions

[edit]

Kinase insert domain receptor has been shown tointeract withSHC2,^[6]Annexin A5^[7] andSHC1.^[8]^[9]

References

[edit]

^^a ^b ^cGRCh38: Ensembl release 89: ENSG00000128052 –Ensembl, May 2017
^^a ^b ^cGRCm38: Ensembl release 89: ENSMUSG00000062960 –Ensembl, May 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.
^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 (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.Bibcode:1999BBRC..258..713W.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 (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.

External links

[edit]

Kinase+insert+domain+receptor at the U.S. National Library of MedicineMedical Subject Headings (MeSH)
Overview of all the structural information available in thePDB forUniProt:P35968 (Vascular endothelial growth factor receptor 2) at thePDBe-KB.

This article incorporates text from theUnited States National Library of Medicine, which is in thepublic domain.

v t e PDB gallery
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

v t e Proteins:clusters of differentiation (see alsolist of human clusters of differentiation)
1–50	CD1 a-c 1A 1B 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50
51–100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 -CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101–150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151–200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201–250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 -CD248 CD249
251–300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301–350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD327 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

Receptors:growth factor receptors

Type I cytokine receptor

Receptor protein serine/threonine kinase

Receptor tyrosine kinase

Fibroblast growth factor 1 2 3 4
Nerve growth factors:high affinityTrk TrkA TrkB TrkC
Hepatocyte growth factor
Somatomedin Insulin-like growth factor 1
ErbB/Epidermal growth factor
VEGF 1 2 3

Tumor necrosis factor receptor

Nerve growth factors:Low affinity/p75

Ig superfamily

Other/ungrouped

Somatomedin
- Insulin-like growth factor 2

Protein kinases:tyrosine kinases (EC 2.7.10)

Receptor tyrosine kinases (EC 2.7.10.1)

Growth factor receptors

EGF receptor family	EGFR ERBB2 ERBB3 ERBB4
Insulin receptor family	IGF1R INSR INSRR
PDGF receptor family	CSF1R FLT3 KIT PDGFR (PDGFRA PDGFRB)
FGF receptor family	FGFR1 FGFR2 FGFR3 FGFR4
VEGF receptors family	VEGFR1 VEGFR2 VEGFR3
HGF receptor family	MET RON
Trk receptor family	NTRK1 NTRK2 NTRK3

EPH receptor family

LTK receptor family

TIE receptor family

ROR receptor family

DDR receptor family

PTK7 receptor family

PTK7

RYK receptor family

MuSK receptor family

MUSK

ROS receptor family

ROS1

AATYK receptor family

AXL receptor family

RET receptor family

uncategorised

STYK1

Non-receptor tyrosine kinases (EC 2.7.10.2)

ABL family	ABL1 ARG
ACK family	ACK1 TNK1
CSK family	CSK MATK
FAK family	FAK PYK2
FES family	FES FER
FRK family	FRK BRK SRMS
JAK family	JAK1 JAK2 JAK3 TYK2
SRC-A family	SRC FGR FYN YES1
SRC-B family	BLK HCK LCK LYN
TEC family	TEC BMX BTK ITK TXK
SYK family	SYK ZAP70

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1Oxidoreductases (list) EC2Transferases (list) EC3Hydrolases (list) EC4Lyases (list) EC5Isomerases (list) EC6Ligases (list) EC7Translocases (list)

Growth factor receptor modulators

Angiopoietin

Agonists:Angiopoietin 1
Angiopoietin 4

Antagonists:Angiopoietin 2
Angiopoietin 3

Kinase inhibitors:Altiratinib
CE-245677
Rebastinib

Antibodies:Evinacumab (against angiopoietin 3)
Nesvacumab (against angiopoietin 2)

CNTF

EGF (ErbB)

EGF (ErbB1/HER1)	Agonists:Amphiregulin Betacellulin EGF (urogastrone) Epigen Epiregulin Heparin-binding EGF-like growth factor (HB-EGF) Murodermin Nepidermin Transforming growth factor alpha (TGFα) Kinase inhibitors:Afatinib Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154 Antibodies:Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab
ErbB2/HER2	Agonists:Unknown/none Antibodies:Ertumaxomab Pertuzumab Trastuzumab Trastuzumab deruxtecan Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors:Afatinib Lapatinib Mubritinib Neratinib Tucatinib
ErbB3/HER3	Agonists:Neuregulins (heregulins) (1,2,6 (neuroglycan C)) Antibodies:Duligotumab Patritumab Seribantumab
ErbB4/HER4	Agonists:Betacellulin Epigen Heparin-binding EGF-like growth factor (HB-EGF) Neuregulins (heregulins) (1,2,3,4,5 (tomoregulin, TMEFF))

FGF

FGFR1	Agonists:Ersofermin FGF (1,2 (bFGF),3,4,5,6,8,10 (KGF2),20) Repifermin Selpercatinib Trafermin Velafermin
FGFR2	Agonists:Ersofermin FGF (1,2 (bFGF),3,4,5,6,7 (KGF),8,9,10 (KGF2),17,18,22) Palifermin Repifermin Selpercatinib Sprifermin Trafermin Antibodies:Aprutumab Aprutumab ixadotin Kinase inhibitors:Infigratinib
FGFR3	Agonists:Ersofermin FGF (1,2 (bFGF),4,8,9,18,23) Selpercatinib Sprifermin Trafermin Antibodies:Burosumab (against FGF23)
FGFR4	Agonists:Ersofermin FGF (1,2 (bFGF),4,6,8,9,19) Trafermin
Unsorted	Agonists:FGF15/19

HGF (c-Met)

Agonists:Fosgonimeton
Hepatocyte growth factor

Potentiators:Dihexa (PNB-0408)

IGF

IGF-1	Agonists:des(1-3)IGF-1 Insulin-like growth factor-1 (somatomedin C) IGF-1 LR3 Insulin-like growth factor-2 (somatomedin A) Insulin Mecasermin Mecasermin rinfabate Kinase inhibitors:BMS-754807 Linsitinib NVP-ADW742 NVP-AEW541 OSl-906 Antibodies:AVE-1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Xentuzumab (against IGF-1 and IGF-2)
IGF-2	Agonists:Insulin-like growth factor-2 (somatomedin A) Antibodies:Dusigitumab Xentuzumab (against IGF-1 and IGF-2)
Others	Binding proteins:IGFBP (1,2,3,4,5,6,7) Cleavage products/derivatives with unknown target:Glypromate (GPE, (1-3)IGF-1) Trofinetide

LNGF (p75^NTR)

Antibodies:Against NGF:ABT-110 (PG110)
ASP-6294
Fasinumab
Frunevetmab
Fulranumab
MEDI-578
Ranevetmab
Tanezumab

Aptamers:Against NGF:RBM-004

Decoy receptors:LEVI-04 (p75^NTR-Fc)

PDGF

Agonists:Becaplermin
Platelet-derived growth factor (A,B,C,D)

RET (GFL)

GFRα1	Agonists:Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors:Vandetanib
GFRα2	Agonists:Neurturin (NRTN) Kinase inhibitors:Vandetanib
GFRα3	Agonists:Artemin (ARTN) Kinase inhibitors:Vandetanib
GFRα4	Agonists:Persephin (PSPN) Kinase inhibitors:Vandetanib
Unsorted	Kinase inhibitors:Agerafenib

SCF (c-Kit)

Agonists:Ancestim
Stem cell factor

TGFβ

Seehere instead.

Trk

TrkA	Agonists:Amitriptyline BNN-20 BNN-27 Cenegermin DHEA DHEA-S Gambogic amide NGF Tavilermide Antagonists:ALE-0540 Dexamethasone FX007 Testosterone Negative allosteric modulators:VM-902A Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib Milciclib ONO-4474 ONO-5390556 PLX-7486 Rebastinib SNA-120 (pegylated K252a)) Antibodies:Against TrkA:GBR-900;Against NGF:ABT-110 (PG110) ASP-6294 Fasinumab Frunevetmab Fulranumab MEDI-578 Ranevetmab Tanezumab Aptamers:Against NGF:RBM-004 Decoy receptors:ReN-1820 (TrkAd5)
TrkB	Agonists:3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF BNN-20 Deoxygedunin Deprenyl Diosmetin DMAQ-B1 HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 R13 TDP6 Antagonists:ANA-12 Cyclotraxin B Gossypetin (3,5,7,8,3',4'-HHF) Ligands:DHEA Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486
TrkC	Agonists:BNN-20 DHEA NT-3 Kinase inhibitors:Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486