VGFR2_COTJA
ID VGFR2_COTJA Reviewed; 1348 AA.
AC P52583;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Vascular endothelial growth factor receptor 2 {ECO:0000250|UniProtKB:P35968};
DE Short=VEGFR-2;
DE EC=2.7.10.1 {ECO:0000250|UniProtKB:P35968};
DE AltName: Full=Endothelial kinase receptor EK1;
DE AltName: Full=Quek 1;
DE Short=Quek1;
DE Flags: Precursor;
GN Name=KDR {ECO:0000250|UniProtKB:P35968}; Synonyms=EK1, FLK-1;
OS Coturnix japonica (Japanese quail) (Coturnix coturnix japonica).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Perdicinae; Coturnix.
OX NCBI_TaxID=93934;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryo;
RX PubMed=8863722; DOI=10.1016/0378-1119(96)00159-x;
RA Eichmann A., Marcelle C., Breant C., Le Douarin N.M.;
RT "Molecular cloning of Quek 1 and 2, two quail vascular endothelial growth
RT factor (VEGF) receptor-like molecules.";
RL Gene 174:3-8(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 910-1348.
RC TISSUE=Spinal cord;
RX PubMed=8396413; DOI=10.1016/0925-4773(93)90096-g;
RA Eichmann A., Marcelle C., Breant C., Le Douarin N.M.;
RT "Two molecules related to the VEGF receptor are expressed in early
RT endothelial cells during avian embryonic development.";
RL Mech. Dev. 42:33-48(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 764-880, AND CHARACTERIZATION.
RC TISSUE=Embryo;
RX PubMed=7781909; DOI=10.1006/dbio.1995.1180;
RA Flamme I., Breier G., Risau W.;
RT "Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (flk-1) are
RT expressed during vasculogenesis and vascular differentiation in the quail
RT embryo.";
RL Dev. Biol. 169:699-712(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1023-1079.
RX PubMed=1281306;
RA Marcelle C., Eichmann A.;
RT "Molecular cloning of a family of protein kinase genes expressed in the
RT avian embryo.";
RL Oncogene 7:2479-2487(1992).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor
CC for VEGFA, VEGFC and/or VEGFD and plays an essential role in the
CC regulation of angiogenesis and vascular development. Promotes
CC proliferation, survival, migration and differentiation of endothelial
CC cells. Promotes reorganization of the actin cytoskeleton. Binding of
CC vascular growth factors leads to the activation of several signaling
CC cascades. Activation of PLCG1 leads to the production of the cellular
CC signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and
CC the activation of protein kinase C. Mediates activation of MAPK1/ERK2,
CC MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1
CC signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory
CC subunit of phosphatidylinositol 3-kinase, reorganization of the actin
CC cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated
CC induction of NOS2 and NOS3, leading to the production of the signaling
CC molecule nitric oxide (NO) by endothelial cells (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. Binding of VEGFA, VEGFC or VEGFD leads to dimerization
CC and activation by autophosphorylation on tyrosine residues (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Cytoplasmic vesicle {ECO:0000250}.
CC Early endosome {ECO:0000250}. Cell junction {ECO:0000250}. Endoplasmic
CC reticulum {ECO:0000250|UniProtKB:P35968}. Note=Detected on caveolae-
CC enriched lipid rafts at the cell surface. Is recycled from the plasma
CC membrane to endosomes and back again. Phosphorylation triggered by
CC VEGFA binding promotes internalization and subsequent degradation.
CC Localized with RAP1A at cell-cell junctions (By similarity).
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: In all endothelial tissues during onset of
CC vascularization. In later development, present in lung, heart,
CC intestine and skin.
CC -!- DEVELOPMENTAL STAGE: Expressed in whole mesoderm at onset of
CC gastrulation. From day 2, confined to endothelial tissues and
CC expression continues to be widespread throughout vascularization until
CC E9 where it becomes restricted to specific regions such as the spinal
CC cord and heart valves.
CC -!- INDUCTION: In vitro, it is induced by basic fibroblast growth factor
CC (bFGF), uniquely in the first 24 hours of cell culture.
CC -!- DOMAIN: The second and third Ig-like C2-type (immunoglobulin-like)
CC domains are sufficient for VEGF binding. {ECO:0000250}.
CC -!- PTM: Autophosphorylated on tyrosine residues upon ligand binding.
CC Autophosphorylation occurs in trans, i.e. one subunit of the dimeric
CC receptor phosphorylates tyrosine residues on the other subunit (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; X83288; CAA58268.1; -; mRNA.
DR EMBL; S65205; AAB28127.1; -; mRNA.
DR EMBL; S78345; AAB34594.1; -; mRNA.
DR PIR; JC4953; S51656.
DR AlphaFoldDB; P52583; -.
DR BMRB; P52583; -.
DR SMR; P52583; -.
DR DIP; DIP-450N; -.
DR BRENDA; 2.7.10.1; 1673.
DR Proteomes; UP000694412; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019838; F:growth factor binding; IEA:InterPro.
DR GO; GO:0005021; F:vascular endothelial growth factor receptor activity; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 7.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS.
DR InterPro; IPR041348; VEGFR-2_TMD.
DR InterPro; IPR009136; VEGFR2_rcpt.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF17988; VEGFR-2_TMD; 1.
DR PRINTS; PR01834; VEGFRECEPTR2.
DR SMART; SM00409; IG; 7.
DR SMART; SM00408; IGc2; 4.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 7.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 5.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; ATP-binding; Cell junction; Cell membrane;
KW Cytoplasmic vesicle; Developmental protein; Differentiation;
KW Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein;
KW Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..1348
FT /note="Vascular endothelial growth factor receptor 2"
FT /id="PRO_0000016774"
FT TOPO_DOM 21..756
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 757..777
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 778..1348
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 43..106
FT /note="Ig-like C2-type 1"
FT DOMAIN 138..202
FT /note="Ig-like C2-type 2"
FT DOMAIN 220..312
FT /note="Ig-like C2-type 3"
FT DOMAIN 320..405
FT /note="Ig-like C2-type 4"
FT DOMAIN 412..534
FT /note="Ig-like C2-type 5"
FT DOMAIN 540..651
FT /note="Ig-like C2-type 6"
FT DOMAIN 658..744
FT /note="Ig-like C2-type 7"
FT DOMAIN 825..1155
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 958..983
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1280..1302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 958..972
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1021
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 831..839
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 859
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1047
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1052
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1168
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1207
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 43
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 47
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 201
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 365
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 386
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 513
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 556
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 603
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 613
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 622
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 666
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 688
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 710
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 50..100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 145..195
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 241..299
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 436..520
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 561..633
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 679..728
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 865
FT /note="A -> S (in Ref. 3; AAB34594)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1348 AA; 150306 MW; A5E4194A76FD5FB3 CRC64;
MELGPLRVLT VLLCLAPVFA GLFISMDQPT LSIQKSVLTI TTNDTLNITC SGQRAVYWSW
PNNQSSVEKR LAVTGCSEGP FCKTLTLLRV IGNDTGDYRC LYGDSQAATT IYVYVQDYRS
PFVTSVGDQL GIVYITKNKT VVVPCLGTVS NLNVSLHAKY PEKVFVPDGK SISWDNKKGF
TIPSHLINYA GMVFCEAKID NESYQSVIYI VAVVGYRIYD LTMNPHYQVE LAVGEKLVLN
CTVRTELNVG IDFRWDYPSI KERRATIRDL KTTAGEIKTF VSTLTIESVN LSDKGRYTCA
ASSGRMNMKN SSYFIIHESP FIHLEKMENV VEMKLGDTVS IPVKFKGYPP PEAKWYKNGK
VINANHTVKL GYALVITEAT EKDAGNYTVV LTNPTNKMQK RHTFTLLVNV PPQIGENALM
APVDSYKYGS TQALTCTIYA VPPPAAVLWY WQLEEECTFS PQKVRLGANP YACRKWKVIS
ERKGGNQVEI KQRVVTIAGK TKTVSTLVIQ AANVSALYRC MATNRAGSSE RVISFHVTRG
LEINLQPRSQ LTEKDNTSLQ CTADKFTFEK LSWYKLSTHV SQTPFGGLPM PVCKNLDALQ
KLNATVSNVN GENVTLELIL RNISLQDGGD YVCIAQDKKA KTQHCLVKHL TVQEPLHPRL
VGNLENQTTN IGETIEVLCT VNGVPPPNIT WFKNSETLFE DSGIVLKDGN KTLTIRRVRK
EDGGLYTCLA CNILGCKKAE AFFSVQGAEE KTNLELIILV GTAVIAMFFW LLLVIILRTV
KRANGGDMKT GYLSIIMDPD EVPIDEHCER LPYDASKWEF PRDRLKLGKP LGRGAFGQVI
EADAFGIDKT ATCRTVAVKM LKEGATHSEH RALMSELKIL IHIGHHLNVV NLLGACTKPG
GPLMVIVEYC KFGNLSAYLR SKRSEFIPYK MKSARFRQGK ENYTGDISTD LKQRLDSITS
SQSSTSSGFV EERSLSDVEE EDAGSEDLCK NPLTMEDLIC YSFQVARGME FLASRKCIHR
DLAARNILLS DNNVVKICDF GLARDIYKDP DYVRKGDARL PLKWMAPETI FDRVYTIQSD
VWSFGVLLWE IFSLGASPYP GVKIDEEFCR RLKEGTRMRA PDYTTPEMYQ TMLDCWHGDP
KQRPTFSELV EHLGNLLQAN VRQDGKDYVV LPLSVSLNME EDSGLSLPTS PASCKEEEEV
CDPKFHYDNT AGISQYRQGS KRKSRPVSVK TFEDIPLVTT VKVVQEENQT DSGMVLASEE
LKTLEEQDKQ VKIPFSTLAP SKSNESVMSE ASNQTSGYQS GYHSDDMDNM VCSSEDTELL
CAQEASPTLP RCAWPGIYSP APVASLPL
