ID VGFR2_HUMAN Reviewed; 1356 AA. AC P35968; O60723; Q14178; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 2. DT 21-SEP-2011, entry version 135. DE RecName: Full=Vascular endothelial growth factor receptor 2; DE Short=VEGFR-2; DE EC=2.7.10.1; DE AltName: Full=Fetal liver kinase 1; DE Short=FLK-1; DE AltName: Full=Kinase insert domain receptor; DE AltName: Full=Protein-tyrosine kinase receptor flk-1; DE AltName: CD_antigen=CD309; DE Flags: Precursor; GN Name=KDR; Synonyms=FLK1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Yin L.Y., Wu Y., Patterson C.; RT "Full length human KDR/flk-1 sequence."; RL Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Umbilical vein; RA Yu Y., Whitney R.G., Sato J.D.; RT "Coding region for human VEGF receptor KDR (VEGFR-2)."; RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-1356, AND VARIANT GLU-848. RC TISSUE=Umbilical vein; RX MEDLINE=92019839; PubMed=1656371; RA Terman B.I., Carrion M.E., Kovacs E., Rasmussen B.A., Eddy R.L., RA Shows T.B.; RT "Identification of a new endothelial cell growth factor receptor RT tyrosine kinase."; RL Oncogene 6:1677-1683(1991). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22. RX MEDLINE=96032749; PubMed=7559454; DOI=10.1074/jbc.270.39.23111; RA Patterson C., Perrella M.A., Hsieh C.-M., Yoshizumi M., Lee M.-E., RA Harber E.; RT "Cloning and functional analysis of the promoter for KDR/flk-1, a RT receptor for vascular endothelial growth factor."; RL J. Biol. Chem. 270:23111-23118(1995). RN [6] RP FUNCTION. RX MEDLINE=93038639; PubMed=1417831; DOI=10.1016/0006-291X(92)90483-2; RA Terman B.I., Dougher-Vermazen M., Carrion M.E., Dimitrov D., RA Armellino D.C., Gospodarowicz D., Boehlen P.; RT "Identification of the KDR tyrosine kinase as a receptor for vascular RT endothelial cell growth factor."; RL Biochem. Biophys. Res. Commun. 187:1579-1586(1992). RN [7] RP INTERACTION WITH HIV-1 TAT. RX PubMed=10590123; DOI=10.1128/JVI.74.1.344-353.2000; RA Mitola S., Soldi R., Zanon I., Barra L., Gutierrez M.I., Berkhout B., RA Giacca M., Bussolino F.; RT "Identification of specific molecular structures of human RT immunodeficiency virus type 1 Tat relevant for its biological effects RT on vascular endothelial cells."; RL J. Virol. 74:344-353(2000). RN [8] RP INTERACTION WITH SHB. RX PubMed=15026417; DOI=10.1074/jbc.M312729200; RA Holmqvist K., Cross M.J., Rolny C., Haegerkvist R., Rahimi N., RA Matsumoto T., Claesson-Welsh L., Welsh M.; RT "The adaptor protein shb binds to tyrosine 1175 in vascular RT endothelial growth factor (VEGF) receptor-2 and regulates VEGF- RT dependent cellular migration."; RL J. Biol. Chem. 279:22267-22275(2004). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1054 AND TYR-1059, AND RP MASS SPECTROMETRY. RC TISSUE=Lung carcinoma; RX PubMed=18083107; DOI=10.1016/j.cell.2007.11.025; RA Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., RA Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., RA Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., RA Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., RA Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; RT "Global survey of phosphotyrosine signaling identifies oncogenic RT kinases in lung cancer."; RL Cell 131:1190-1203(2007). RN [10] RP PHOSPHORYLATION AT TYR-951; TYR-1175 AND TYR-1214, AND RP DEPHOSPHORYLATION BY PTPRB. RX PubMed=19136612; DOI=10.1096/fj.08-123810; RA Mellberg S., Dimberg A., Bahram F., Hayashi M., Rennel E., Ameur A., RA Westholm J.O., Larsson E., Lindahl P., Cross M.J., Claesson-Welsh L.; RT "Transcriptional profiling reveals a critical role for tyrosine RT phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial RT cell morphogenesis."; RL FASEB J. 23:1490-1502(2009). RN [11] RP PHOSPHORYLATION AT TYR-801; TYR-951; TYR-996; TYR-1054; TYR-1059; RP TYR-1175 AND TYR-1214; DEPHOSPHORYLATION BY PTPRJ AT TYR-951; TYR-996; RP TYR-1054; TYR-1059; TYR-1175 AND TYR-1214. RX PubMed=18936167; DOI=10.1128/MCB.01374-08; RA Chabot C., Spring K., Gratton J.P., Elchebly M., Royal I.; RT "New role for the protein tyrosine phosphatase DEP-1 in Akt activation RT and endothelial cell survival."; RL Mol. Cell. Biol. 29:241-253(2009). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 806-1171, FUNCTION, RP PHOSPHORYLATION AT TYR-1059, AND MASS SPECTROMETRY. RX PubMed=10368301; DOI=10.1016/S0969-2126(99)80042-2; RA McTigue M.A., Wickersham J.A., Pinko C., Showalter R.E., Parast C.V., RA Tempczyk-Russell A., Gehring M.R., Mroczkowski B., Kan C.-C., RA Villafranca J.E., Appelt K.; RT "Crystal structure of the kinase domain of human vascular endothelial RT growth factor receptor 2: a key enzyme in angiogenesis."; RL Structure 7:319-330(1999). RN [13] RP X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) OF 806-1171 IN COMPLEX WITH RP SYNTHETIC INHIBITOR. RX PubMed=15837294; DOI=10.1016/j.bmcl.2005.03.034; RA Miyazaki Y., Matsunaga S., Tang J., Maeda Y., Nakano M., RA Philippe R.J., Shibahara M., Liu W., Sato H., Wang L., Nolte R.T.; RT "Novel 4-amino-furo[2,3-d]pyrimidines as Tie-2 and VEGFR2 dual RT inhibitors."; RL Bioorg. Med. Chem. Lett. 15:2203-2207(2005). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 815-1171 IN COMPLEX WITH RP SYNTHETIC INHIBITOR. RX PubMed=17253678; DOI=10.1021/jm061107l; RA Hodous B.L., Geuns-Meyer S.D., Hughes P.E., Albrecht B.K., Bellon S., RA Bready J., Caenepeel S., Cee V.J., Chaffee S.C., Coxon A., Emery M., RA Fretland J., Gallant P., Gu Y., Hoffman D., Johnson R.E., Kendall R., RA Kim J.L., Long A.M., Morrison M., Olivieri P.R., Patel V.F., RA Polverino A., Rose P., Tempest P., Wang L., Whittington D.A., Zhao H.; RT "Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5- RT triazine Tie-2 kinase inhibitor."; RL J. Med. Chem. 50:611-626(2007). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 806-1171 IN COMPLEX WITH RP SYNTHETIC INHIBITOR, AND FUNCTION. RX PubMed=18529047; DOI=10.1021/jm8001185; RA Peifer C., Selig R., Kinkel K., Ott D., Totzke F., Schaechtele C., RA Heidenreich R., Roecken M., Schollmeyer D., Laufer S.; RT "Design, synthesis, and biological evaluation of novel 3-aryl-4-(1H- RT indole-3yl)-1,5-dihydro-2H-pyrrole-2-ones as vascular endothelial RT growth factor receptor (VEGF-R) inhibitors."; RL J. Med. Chem. 51:3814-3824(2008). RN [16] RP VARIANT HCI SER-1147. RX PubMed=11807987; DOI=10.1002/gcc.10028; RA Walter J.W., North P.E., Waner M., Mizeracki A., Blei F., RA Walker J.W.T., Reinisch J.F., Marchuk D.A.; RT "Somatic mutation of vascular endothelial growth factor receptors in RT juvenile hemangioma."; RL Genes Chromosomes Cancer 33:295-303(2002). RN [17] RP VARIANTS [LARGE SCALE ANALYSIS] LEU-275 AND ARG-873. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). RN [18] RP VARIANTS [LARGE SCALE ANALYSIS] ARG-2; MET-136; GLY-248; ILE-297; RP VAL-462; HIS-472; ARG-482; ARG-539; MET-689; ASN-814 AND THR-1065. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [19] RP VARIANT HCI SUSCEPTIBILITY ARG-482. RX PubMed=18931684; DOI=10.1038/nm.1877; RA Jinnin M., Medici D., Park L., Limaye N., Liu Y., Boscolo E., RA Bischoff J., Vikkula M., Boye E., Olsen B.R.; RT "Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 RT signaling in infantile hemangioma."; RL Nat. Med. 14:1236-1246(2008). CC -!- FUNCTION: Receptor for VEGF or VEGFC. Has a tyrosine-protein CC kinase activity. The VEGF-kinase ligand/receptor signaling system CC plays a key role in vascular development and regulation of CC vascular permeability. In case of HIV-1 infection, the interaction CC with extracellular viral Tat protein seems to enhance angiogenesis CC in Kaposi's sarcoma lesions. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. CC -!- SUBUNIT: Interacts with MYOF (By similarity). Interacts with SHB; CC upon VEGF activation. Interacts with HIV-1 Tat. CC -!- INTERACTION: CC P35916:FLT4; NbExp=3; IntAct=EBI-1005487, EBI-1005467; CC P12931:SRC; NbExp=2; IntAct=EBI-1005487, EBI-621482; CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC protein. CC -!- PTM: Phosphorylated. Dephosphorylated by PTPRB. Dephosphorylated CC by PTPRJ at Tyr-951, Tyr-996, Tyr-1054, Tyr-1059, Tyr-1175 and CC Tyr-1214. CC -!- DISEASE: Defects in KDR are associated with susceptibility to CC hemangioma capillary infantile (HCI) [MIM:602089]. HCI are benign, CC highly proliferative lesions involving aberrant localized growth CC of capillary endothelium. They are the most common tumor of CC infancy, occurring in up to 10% of all births. Hemangiomas tend to CC appear shortly after birth and show rapid neonatal growth for up CC to 12 months characterized by endothelial hypercellularity and CC increased numbers of mast cells. This phase is followed by slow CC involution at a rate of about 10% per year and replacement by CC fibrofatty stroma. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. CSF-1/PDGF receptor subfamily. CC -!- SIMILARITY: Contains 7 Ig-like C2-type (immunoglobulin-like) CC domains. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF035121; AAB88005.1; -; mRNA. DR EMBL; AF063658; AAC16450.1; -; mRNA. DR EMBL; AC021220; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC111194; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; L04947; AAA59459.1; -; mRNA. DR EMBL; X61656; CAA43837.1; -; mRNA. DR EMBL; X89776; CAA61916.1; -; Genomic_DNA. DR IPI; IPI00021396; -. DR PIR; JC1402; JC1402. DR RefSeq; NP_002244.1; NM_002253.2. DR UniGene; Hs.479756; -. DR PDB; 1VR2; X-ray; 2.40 A; A=806-1171. DR PDB; 1Y6A; X-ray; 2.10 A; A=806-1171. DR PDB; 1Y6B; X-ray; 2.10 A; A=806-1171. DR PDB; 1YWN; X-ray; 1.71 A; A=806-1171. DR PDB; 2OH4; X-ray; 2.05 A; A=806-1171. DR PDB; 2P2H; X-ray; 1.95 A; A=815-1171. DR PDB; 2P2I; X-ray; 2.40 A; A/B=815-1171. DR PDB; 2QU5; X-ray; 2.95 A; A=815-1171. DR PDB; 2QU6; X-ray; 2.10 A; A/B=815-1171. DR PDB; 2RL5; X-ray; 2.65 A; A=815-1171. DR PDB; 2X1W; X-ray; 2.70 A; L/M/N/O=120-326. DR PDB; 2X1X; X-ray; 3.10 A; R=120-326. DR PDB; 2XIR; X-ray; 1.50 A; A=806-1171. DR PDB; 3B8Q; X-ray; 2.75 A; A/B=815-1171. DR PDB; 3B8R; X-ray; 2.70 A; A/B=815-1171. DR PDB; 3BE2; X-ray; 1.75 A; A=815-1171. DR PDB; 3C7Q; X-ray; 2.10 A; A=806-1171. DR PDB; 3CJF; X-ray; 2.15 A; A=806-1168. DR PDB; 3CJG; X-ray; 2.25 A; A=806-1168. DR PDB; 3CP9; X-ray; 2.50 A; A/B=815-1171. DR PDB; 3CPB; X-ray; 2.70 A; A/B=815-1171. DR PDB; 3CPC; X-ray; 2.40 A; A/B=815-1171. DR PDB; 3DTW; X-ray; 2.90 A; A/B=815-1171. DR PDB; 3EFL; X-ray; 2.20 A; A/B=815-1171. DR PDB; 3EWH; X-ray; 1.60 A; A=815-1171. DR PDB; 3KVQ; X-ray; 2.70 A; A=657-764. DR PDBsum; 1VR2; -. DR PDBsum; 1Y6A; -. DR PDBsum; 1Y6B; -. DR PDBsum; 1YWN; -. DR PDBsum; 2OH4; -. DR PDBsum; 2P2H; -. DR PDBsum; 2P2I; -. DR PDBsum; 2QU5; -. DR PDBsum; 2QU6; -. DR PDBsum; 2RL5; -. DR PDBsum; 2X1W; -. DR PDBsum; 2X1X; -. DR PDBsum; 2XIR; -. DR PDBsum; 3B8Q; -. DR PDBsum; 3B8R; -. DR PDBsum; 3BE2; -. DR PDBsum; 3C7Q; -. DR PDBsum; 3CJF; -. DR PDBsum; 3CJG; -. DR PDBsum; 3CP9; -. DR PDBsum; 3CPB; -. DR PDBsum; 3CPC; -. DR PDBsum; 3DTW; -. DR PDBsum; 3EFL; -. DR PDBsum; 3EWH; -. DR PDBsum; 3KVQ; -. DR ProteinModelPortal; P35968; -. DR SMR; P35968; 35-119, 122-461, 521-550, 560-756, 815-1171. DR DIP; DIP-486N; -. DR DIP; DIP-5741N; -. DR IntAct; P35968; 5. DR MINT; MINT-127732; -. DR STRING; P35968; -. DR PhosphoSite; P35968; -. DR PRIDE; P35968; -. DR Ensembl; ENST00000263923; ENSP00000263923; ENSG00000128052. DR GeneID; 3791; -. DR KEGG; hsa:3791; -. DR UCSC; uc003has.1; human. DR CTD; 3791; -. DR GeneCards; GC04M051893; -. DR H-InvDB; HIX0031357; -. DR HGNC; HGNC:6307; KDR. DR HPA; CAB004028; -. DR MIM; 191306; gene. DR MIM; 602089; phenotype. DR neXtProt; NX_P35968; -. DR Orphanet; 91415; Familial capillary hemangioma. DR PharmGKB; PA30086; -. DR HOVERGEN; HBG053432; -. DR InParanoid; P35968; -. DR OMA; QDYRSPF; -. DR OrthoDB; EOG48KR9F; -. DR PhylomeDB; P35968; -. DR BRENDA; 2.7.10.1; 2681. DR Pathway_Interaction_DB; avb3_integrin_pathway; Integrins in angiogenesis. DR Pathway_Interaction_DB; s1p_s1p1_pathway; S1P1 pathway. DR Pathway_Interaction_DB; vegfr1_2_pathway; Signaling events mediated by VEGFR1 and VEGFR2. DR Reactome; REACT_12529; Signaling by VEGF. DR DrugBank; DB00398; Sorafenib. DR DrugBank; DB01268; Sunitinib. DR NextBio; 14887; -. DR ArrayExpress; P35968; -. DR Bgee; P35968; -. DR CleanEx; HS_KDR; -. DR Genevestigator; P35968; -. DR GermOnline; ENSG00000128052; Homo sapiens. DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019838; F:growth factor binding; IPI:BHF-UCL. DR GO; GO:0051879; F:Hsp90 protein binding; TAS:BHF-UCL. DR GO; GO:0005178; F:integrin binding; IPI:BHF-UCL. DR GO; GO:0004716; F:receptor signaling protein tyrosine kinase activity; TAS:BHF-UCL. DR GO; GO:0005021; F:vascular endothelial growth factor receptor activity; IDA:BHF-UCL. DR GO; GO:0001525; P:angiogenesis; TAS:BHF-UCL. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0044419; P:interspecies interaction between organisms; IEA:UniProtKB-KW. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:BHF-UCL. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:BHF-UCL. DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IDA:BHF-UCL. DR GO; GO:0050927; P:positive regulation of positive chemotaxis; IDA:BHF-UCL. DR GO; GO:0008360; P:regulation of cell shape; IDA:BHF-UCL. DR InterPro; IPR007110; Ig-like. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR013106; Ig_V-set. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_cat_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS. DR InterPro; IPR009136; Tyr_kinase_VEGFR2_rcpt. DR InterPro; IPR009134; Tyr_kinase_VEGFR_rcpt_N. DR Gene3D; G3DSA:2.60.40.10; Ig-like_fold; 8. DR Pfam; PF07679; I-set; 2. DR Pfam; PF07714; Pkinase_Tyr; 1. DR Pfam; PF07686; V-set; 1. DR PRINTS; PR01832; VEGFRECEPTOR. DR PRINTS; PR01834; VEGFRECEPTR2. DR SMART; SM00409; IG; 4. DR SMART; SM00408; IGc2; 2. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF56112; Kinase_like; 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 3D-structure; Angiogenesis; ATP-binding; Complete proteome; KW Developmental protein; Differentiation; Glycoprotein; KW Host-virus interaction; Immunoglobulin domain; Kinase; Membrane; KW Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor; KW Reference proteome; Repeat; Signal; Transferase; Transmembrane; KW Transmembrane helix; Tyrosine-protein kinase. FT SIGNAL 1 19 Potential. FT CHAIN 20 1356 Vascular endothelial growth factor FT receptor 2. FT /FTId=PRO_0000016771. FT TOPO_DOM 20 764 Extracellular (Potential). FT TRANSMEM 765 789 Helical; (Potential). FT TOPO_DOM 790 1356 Cytoplasmic (Potential). FT DOMAIN 46 110 Ig-like C2-type 1. FT DOMAIN 141 207 Ig-like C2-type 2. FT DOMAIN 224 320 Ig-like C2-type 3. FT DOMAIN 328 414 Ig-like C2-type 4. FT DOMAIN 421 548 Ig-like C2-type 5. FT DOMAIN 551 660 Ig-like C2-type 6. FT DOMAIN 667 753 Ig-like C2-type 7. FT DOMAIN 834 1162 Protein kinase. FT NP_BIND 840 848 ATP (By similarity). FT ACT_SITE 1028 1028 Proton acceptor (By similarity). FT BINDING 868 868 ATP (By similarity). FT SITE 1175 1175 Interaction with SHB (By similarity). FT MOD_RES 801 801 Phosphotyrosine. FT MOD_RES 951 951 Phosphotyrosine. FT MOD_RES 996 996 Phosphotyrosine. FT MOD_RES 1054 1054 Phosphotyrosine. FT MOD_RES 1059 1059 Phosphotyrosine; by autocatalysis. FT MOD_RES 1175 1175 Phosphotyrosine. FT MOD_RES 1214 1214 Phosphotyrosine. FT CARBOHYD 46 46 N-linked (GlcNAc...) (Potential). FT CARBOHYD 66 66 N-linked (GlcNAc...) (Potential). FT CARBOHYD 96 96 N-linked (GlcNAc...) (Potential). FT CARBOHYD 143 143 N-linked (GlcNAc...) (Potential). FT CARBOHYD 158 158 N-linked (GlcNAc...) (Potential). FT CARBOHYD 245 245 N-linked (GlcNAc...) (Potential). FT CARBOHYD 318 318 N-linked (GlcNAc...) (Potential). FT CARBOHYD 374 374 N-linked (GlcNAc...) (Potential). FT CARBOHYD 395 395 N-linked (GlcNAc...) (Potential). FT CARBOHYD 511 511 N-linked (GlcNAc...) (Potential). FT CARBOHYD 523 523 N-linked (GlcNAc...) (Potential). FT CARBOHYD 580 580 N-linked (GlcNAc...) (Potential). FT CARBOHYD 613 613 N-linked (GlcNAc...) (Potential). FT CARBOHYD 619 619 N-linked (GlcNAc...) (Potential). FT CARBOHYD 631 631 N-linked (GlcNAc...) (Potential). FT CARBOHYD 675 675 N-linked (GlcNAc...) (Potential). FT CARBOHYD 704 704 N-linked (GlcNAc...) (Potential). FT CARBOHYD 721 721 N-linked (GlcNAc...) (Potential). FT VARIANT 2 2 Q -> R (in a lung adenocarcinoma sample; FT somatic mutation). FT /FTId=VAR_042053. FT VARIANT 136 136 V -> M (in dbSNP:rs35636987). FT /FTId=VAR_042054. FT VARIANT 248 248 A -> G (in a renal clear cell carcinoma FT sample; somatic mutation). FT /FTId=VAR_042055. FT VARIANT 275 275 R -> L (in a colorectal cancer sample; FT somatic mutation). FT /FTId=VAR_036126. FT VARIANT 297 297 V -> I (in dbSNP:rs2305948). FT /FTId=VAR_022071. FT VARIANT 462 462 L -> V (in dbSNP:rs56286620). FT /FTId=VAR_042056. FT VARIANT 472 472 Q -> H (in dbSNP:rs1870377). FT /FTId=VAR_020353. FT VARIANT 482 482 C -> R (in HCI susceptibility; expression FT of FLT1 in hemangioma endothelial cells FT is markedly reduced and KDR activity is FT increased compared to controls; low FLT1 FT expression in hemangioma cells is caused FT by reduced activity of a pathway FT involving ITGB1, ANTXR1, KDR and FT NFATC2IP; the mutation predicts to result FT in loss-of-function and disruption of the FT normal association of these molecules; FT dbSNP:rs34231037). FT /FTId=VAR_042057. FT VARIANT 539 539 G -> R (in dbSNP:rs55716939). FT /FTId=VAR_042058. FT VARIANT 689 689 T -> M (in dbSNP:rs34038364). FT /FTId=VAR_042059. FT VARIANT 814 814 D -> N (in dbSNP:rs35603373). FT /FTId=VAR_042060. FT VARIANT 848 848 V -> E (in dbSNP:rs1139776). FT /FTId=VAR_046679. FT VARIANT 873 873 G -> R (in a colorectal cancer sample; FT somatic mutation). FT /FTId=VAR_036127. FT VARIANT 952 952 V -> I (in dbSNP:rs13129474). FT /FTId=VAR_046680. FT VARIANT 1065 1065 A -> T (in dbSNP:rs56302315). FT /FTId=VAR_042061. FT VARIANT 1147 1147 P -> S (in HCI; somatic mutation). FT /FTId=VAR_063147. FT CONFLICT 2 2 Q -> E (in Ref. 2; AAC16450). FT CONFLICT 772 772 A -> T (in Ref. 4; AAA59459/CAA43837). FT CONFLICT 787 787 R -> G (in Ref. 4; AAA59459/CAA43837). FT CONFLICT 835 835 K -> N (in Ref. 4; AAA59459/CAA43837). FT CONFLICT 1347 1347 S -> T (in Ref. 4; AAA59459/CAA43837). FT HELIX 824 827 FT HELIX 831 833 FT STRAND 834 841 FT STRAND 844 855 FT STRAND 858 860 FT STRAND 862 870 FT HELIX 876 892 FT STRAND 901 905 FT STRAND 907 910 FT STRAND 913 917 FT HELIX 924 929 FT TURN 930 933 FT HELIX 1002 1021 FT HELIX 1031 1033 FT STRAND 1034 1036 FT STRAND 1042 1044 FT HELIX 1068 1071 FT HELIX 1074 1077 FT HELIX 1084 1099 FT HELIX 1115 1120 FT HELIX 1133 1142 FT HELIX 1147 1149 FT HELIX 1153 1167 SQ SEQUENCE 1356 AA; 151527 MW; 59E7C44B05CFEBB3 CRC64; 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 //